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- [00:03]
A
Welcome to season three of Derms on Drugs, a video podcast brought to you by Scholars in Medicine, the best educational platform in dermatology and provided a no cost to medical providers. Terms on Drugs is where cutting edge derm meets hit or miss comedy. I'm Matt Zyrush from Docs Dermatology and each week I'm joined by my residency buddies, Dr. Laura Faris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh Medical center. We use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know to be on the cutting edge of derm and you'll have some fun listening. New episodes drop every Friday on Scholars Medicine, Apple Podcasts, Spotify and other major podcast platforms. And I want to tell you guys, I highly recommend getting the Scholars in Medicine app so you can send us questions and comments through the app. And yes, I will actually respond personally. You get the full show repository. Much less importantly, you get the best derm content in existence. So we're talking real content, not pharma driven, covering all of dermatology and supporting by a great Ask Simon AI. If you go in there, the first thing that you go to is the video banker is what it's called and the core curriculum in dermatology has it. Well, it's just, it's phenomenal. And then there's all kinds of new cutting edge content coming out all the time. So let's go ahead and get into it for our episode. We've got a patented six pack episode coming at you today. We're going to start with Dr. Faris, but before we get into that first article, I actually did not watch the game. It's Dr. Faris who won the Duke UNC game over the weekend. Did you guys pull it out?
- [01:45]
B
Oh, you. I know that you watched it and you're just trying to throw me off my game. UNC did not win, unfortunately.
- [01:53]
C
UNC got, got crushed.
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A
Okay. I watched.
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B
They. Did not win. Did not win. We're like down our, you know, top two starters and you know, who won with a full team a few weeks ago, A month ago. Unc.
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C
Okay, tournament's going to be. That's going to be good stuff.
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B
Yeah, it is.
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A
I watch, I watched the pregame, but I had tickets to go see Kevin James, you know, from the King of Queens and Paul Blart and all that stuff. He was, he was good. It was funny.
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C
I thought you were going to say another ABBA cover band.
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A
All right, let's get into. That's enough. Let's get into it. Ferris. Ferris, what do you got?
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B
So I am going to start with kind of two papers, but they were both in jad, both by the same people, both covering the same topic. So this is utility of the 31 gene expression profile for AJCC on cancer PT1Amelanoma. So basically, how does decision DX31 GEP work on T1Amelanomas? Then we'll move on to T1B melanomas. This is Joshi et al, who are at Baylor. Okay, so our favorite thing.
- [03:07]
A
I'm going to interrupt for a second first, Ferris, I do want to tell you, one of our listeners this week told me that literally their favorite thing is when I interrupt you and then you get you. You put me in my place. That they don't like me interrupting. They like you putting me in my place. But just I got to say, I'm also going to be doing a gene expression profiling paper. We need Castle. We need Castle to start sponsoring us. Damn it. Well, it depends what we're going to say, I guess. So let's see. Let's see what we're gonna say. All right, I'll let you go.
- [03:36]
B
Okay, so basically, there's these two. I, I. You know, it's nice to have these two brief reports. One one is focused on T1A. One is focused on T1B. Okay, so let's start up with the T1A paper. So what they did was this was not like, you know, this wasn't a Castle database. So this was a SEER database. So SEAR has Decision DX results linked in their database. So what they have is the Class 1A 1B Class 2A 2B result to seer. Now, I will say that these authors, the first thing I was like, patent is going to be like, everybody's, you know, works for and consults for Castle, blah, blah, blah. No conflicts of interest. Okay. So just putting that.
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A
Okay.
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B
Yeah. Okay.
- [04:26]
C
Patents on board.
- [04:27]
B
Yeah. 33513T1Amelanomas. And then what they did. So the way that they kind of looked at the data, there were some funny things to me, but we'll talk about that some. So the first thing they did was they said, are these low risk or high risk? And so T1As. So low risk meant age over 42, not on the head, neck Breslow 0.5 millimeters or less, mitotic rate under 2 per millimeter square. High risk was sort of like the converse of These. So there were basically 1060 low risks and 2319 high risks. So it does look like, you know, certainly on average most of us would biopsy. Well, more, I would say more low risk T1As. So it does look like this wasn't like across the board, equal use on every T1A. Okay, so what did they find? 95% of low risk T1As and 90.6% of high risk T1As were class 1A overall or were class 1A. So that's 92% of all T1As. So if you're like, you know, this kind of fits with other data that we've seen in other groups which are like pretty much if you're going to send T1As, the vast, vast, vast majority of them are going to come back as low risk. So what does that really mean? So in terms of survival in the low risk T1A group, there were 5% of patients who had that non class 1A result. None of these died of melanoma, probably not shockingly so. So there is no survival analysis in the high risk group. The Class 1B or higher group had a hazard of melanoma specific death. Their hazard of melanoma specific death was higher. Their hazard ratio was 5.72 versus class 1A. And that 95% confidence interval was like, that was statistically significant. Now there were so few in there that when you look at, you know, the table in there, their table one, they just had to call it less than 20 because if you're, if you're great, if you have less than 20, they can't actually give you, for privacy reasons, number. So this is not a huge number of patients. So the other thing that they, you know, is that they're like, that they found, which is not surprising, was that, well, in the high risk T1A group, age over 42 was associated with worse melanoma specific survival hazard ratio of 7.5:1, whereas Breslow depth over 0.5, mitotic rate location on the head and neck were not statistically significant. Proceed predictors. So, you know, the thing is what I don't like about this is the age thing. So this is my big beef on, you know, looking at age and stratifying in sentinel node and risk having being older makes you less likely to have a positive sentinel node. Being older also makes you do have a worse survival with your melanoma. So we know that like we're using like sentinel node in and of itself is not an important outcome. It is important because it is A predictor of survival from melan or basically bad melanoma outcomes, positive node, greater risk of having, you know, distant metastases, death from melanoma, et cetera, et cetera. But older age, lower likelihood of having a sentinel node that's positive. So if you're, you know, so they call it a high risk feature, but it's high risk of a positive node, low risk of death. Okay, so that's my soapbox about that. So you know, they, they also don't capture things like seer. They can only see what SEER captures. So lymphovascular invasion not going to be, you know, counted. The transected melanomas are going to fall, you know, probably in that high risk group. So maybe some of those were actually like 1.5 or 2 millimeter melanomas. So you know, it's also retrospective registry based blood, blah blah, blah. So this kind of gets back to I think what you know, I've always thought, which is that this is not a super helpful test, particularly for like your run of the mill T1Amelanomas. The vast majority of them are going to be low risk and you're really not going to get a lot of additional information.
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A
Okay, all right, so wait, Ferris, can I, can I. Are you done with the first.
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B
Yeah.
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A
Can I ask. Okay, so here's what. So I did not know, shockingly that older people were less likely to have a positive node and more likely to die.
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B
Yes.
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A
What, what does that. I feel like that's one of those things that I was surprised to hear it and therefore it is like telling us something interesting.
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B
You are very smart and so that is why. So I have always wondered that. And then I have, I heard somebody give a talk on this. Jason Luke, who was a medical oncologist, well known melanoma oncologist who used to be at Pitt with us. So it turns out that the lymphatics get leakier the older that we get. Which means that like the, that and they have, you know, data where they've like looked at the technetium and you know how much of the technetium makes it to the draining node in younger ver old people. Your lymphatics like everything else as you get older don't work as well. So the thought is like, you know, a few cells here and there, like you just don't have. It's like you got bad pipes getting you to the lymph node and basically
- [10:25]
A
the melanoma cells leak out.
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B
Can leak out. So you know, probably like if you've got a big honking tumor, that's going to make it in. But if you've got like a couple cells, it's not going to. That the integrity of the lymphatics is not as good.
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A
And that would make some sense in the sense that if the cells don't get to the lymph nodes, you are less likely to generate an immune response to them. And so therefore you're in theory more likely to die from your melanoma because your immune system never got to learn about it in the lymph nodes.
- [11:01]
B
Yeah. And just as you get older you're immunity is, does it is, you know, kind of is impaired as well. So yeah, like everything else, it sucks. So you know, so basically like this is, I think that this age thing is a really important consideration that we say they're younger, do a sentinel node because it's more likely to be positive, but that's a reflection of the integrity of their lymphatics. It's not a reflection of risk. In fact, you know, a 40 year old, you know, and then like what, why, how do we come up with 42. It is in the NCC, NCCN guidelines. It is based on like one retrospective study out of one center that looked at T1Amelanomas that had had sentinel node biopsy and they picked like the 25th percentile among like breaking them down into interquartile ranges. It was a sort of, it was not an, it was based on the data out of one center that was of retrospective stuff. So 42 is not magical. You know, if you look at the Castle data, they'll say, oh, you know, you. This is helpful in predicting risk of a positive sentinel node and patients. I'm going to get the number. I think it's age 55 and older in like an old, an older study that was published in like future oncology. So. Yes. And the reason is that if you look at people younger, they're just more likely to have a positive sentinel note. So yeah, I think that's important to know. Okay.
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A
Okay.
- [12:35]
B
All right, next paper to the T1BS. Okay, so you know, little more anxiety provoking group, the T1BS. So what they did was they looked at whether 31 GEP can help us decide who should actually get a sentinel node biopsy using the same c or decision dx. So what do NCCN guidelines say about T1B? They say discuss and consider. So that's the group where you'd say the probability of a positive Sentinel Notice between 5 and 10% Discuss and consider, not slam dunk. You know, there's shared decision making, think about the patient, blah, blah, blah. So you know, it would be great if it were if you could add in more data like, hey, this is a low risk tumor, you don't need to, you know, do this. And there are decide data which is more of a prospective study, this is retrospective that might suggest that that could be true. But in this analysis, over 1200T1BS, these patients average age was about 60 years old. Just kind of thinking about that. Everything we just talked about mean Breslow Depth 86, 13% were ulcerated. Of these, 57% of patients actually underwent sentinel lymph node biopsies. And among the group, the positivity rate was 11.5%. So 80 patients had a positive node. Now here's the thing. You look at those 80, 66 of them, 82.5% of them actually had a class one low risk GEP result. So that kind of would suggest that, you know, these are the node positive people. And 82% of them have a low risk result. Now there's, you know, what about the people? Only about half of the people who would have been candidates. A little more than half. So interestingly, a little more than half of the people who got the test still ended up, you know, getting a sentinel lymph node. And you know, of those people, so 80 of them actually had a positive note. So it's like, how were people really following this result a whole lot and you know, but there's a group where people decided not to do it. Maybe they were all class 1A. The thing I didn't love about this paper is like, there's no table in there. I want to see the table of like, you know, these are the numbers. This is the number who had a sentinel node. This is what the, you know, the, the breakdown. There's really not a lot of granular data to sort of hypothesize about what is going on. So they said among those who did not undergo sentinel node biopsy, Those with Class 1B or higher had similar melanoma specific survival to those with class 1A. So the people, if you, you know, if you forego the sentinel node biopsy and say, I'll use the GEP result, they really had pretty similar outcomes. The hazard ratio was 2.1. Confidence interval crossed 1 though. So really the data did not say, oh, non Class 1A patients who skip a sentinel node are doing worse. So, you know, take that for what it's worth. So the authors concluded that their data do not support using 31ge to omit sentinel node in T1B. They. They say that there's a Mayo Clinic paper that we actually talked about maybe a few months ago that also did not find this. In fact, the Mayo one found higher node metastases in the low risk G. So, you know, it's. This paper was odd. I just really would have loved a table to break down everything to try to think about it. We also don't know, like, why the test was ordered. Was there, like, was this just people who order in everybody? Were these patients in some reason, for some reason considered to be higher risk, lower risk, bad surgical candidates? We just don't know. And then, you know, why did they get a sentinel node biopsy if the result was class 1A anyway? You know, did they have that IG? We don't know.
- [16:36]
C
We know the answer to those questions because Castle testing is rammed down our throats that we need to do it on every melanoma. That's 0.3. And the reason that 1A still got the sentinel node is because they were like, all right, I'm going to order the Castle testing at the dermatology office before a patient has even talked to an oncologist. They are. They're T1B. So you should have that discussion with an oncologist and a surgeon. And the oncologist and the surgeon were like, we don't. We're ignoring the CASL data. We don't go by that. And they got the Sentinel note on top of it. And this is the problem with the Castle testing. It is done indiscriminately and it's not helpful. And most oncologists and surgeons absolutely ignore Casel stuff because they're like, look, I have seen bad melanomas that were 1A. It's not a reliable test in their hands.
- [17:32]
B
So, yeah, that's my.
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C
Yeah, that's my theory.
- [17:35]
B
I can tell Peter, everybody you like. It's like any other test. Don't order the test unless it's going to guide your decision making. Right. If you're going to say, here it is now, I'm going to send you to oncology and or surgical oncology, and then you're going to get Sentinel Note anyway. Like, was that guiding you? Yes or no? So there have been times that I have used this when I've had the discussion with the, you know, the. The whole team. Right. So we've all agreed to. There's a reason why we want this information. If this. If we get this result, we're going to make this decision, and with this one, we'll make a different decision. But that's, you know. Yeah, it's. The problem is we do it with everybody, then we send them over to the oncology group. Is not a good strategy.
- [18:20]
C
And I think it's totally reasonable. If you had a T1B and you're like, man, that sentinel node. I really don't like the sound of that. Is there any test I could do that maybe would discriminate. Is this really going to be pot? Like, I think at that point, when you've had the discussion with the surgeon and the oncologist and you say, you know what? I. I think I am going to go based on what my Castle score is. Can we order that test? Totally, totally reasonable.
- [18:46]
B
Yeah.
- [18:47]
C
That's just not the way that it's used, and it's not the way Castle wants us to. They. They want us to indiscriminately order it on everybody because that's how they're going to make money, which, again, totally. You got to make money.
- [18:57]
A
It's so patent. But you did not bring out. I know Patton is particularly worked up when he brings out the term steak dinner. That's the, like. When he's like, orders for steak dinners. All right, so I. I'm gonna.
- [19:15]
B
So they do bring up the cost. So this was an interesting number. They said, you know, they. They said, you know, what's the different. Maybe there's cost savings. But they said, using Medicare reimbursement data, $7,193 for the GEP test versus the cost of sentinel node. They said if it's done in an ambulatory surgical center, it's 3470. Or if it's done in a hospital, as a hospital outpatient, it's $6,220. So it's kind of interesting. Both of their. Their sentinel node numbers are less expensive than the GP test now. Everybody doesn't pay for the gp. Insurance companies mark it down, blah, blah, blah. There's all kinds of stuff. So. So.
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A
All right, first, this. I would say Castle testing has gotten too complicated for me so that I actually no longer have a strong opinion on this. So what. How should people use this? Like, what's the. When should somebody order a Castle? Or is it, like, never? Like, according to Patton, the. Like, the oncologist can order it if they want it. I don't want it. Like, Ferris, what's. What's Your. What's your ideal use scenario for Castle testing?
- [20:37]
B
For me, it is one. It is going to change what I am going to do. So if it is you, I'm on the fence about a sentinel node biopsy. Oncology's on the, you know, as a team. We're on the fence about is that needed a little more data would be helpful. That's it. That's a help, that is.
- [20:55]
A
Who's that patient who like what is.
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B
Because I would say it is 90 years old. You've got a big like lentigo malignant melanoma. You've got like, I don't know, maybe it's a millimeter thick. Thick. It's going to be a bear to clear this. You're a bad surgical candidate. That's the person. Like I'm not going to do it on a 35 year old because I know that like it's more likely to come back that they are likely to have a positive node. Right. So a. The younger, when you put in the like the IGEP where they are integrating a bunch of factors like the tumor thickness, the tumor location, the patient age. If I, if you have the same, you know, tumor factors and the patient's 35 versus 81 of them, the 35 year old is probably going to have a risk. Let's say it's a 0.5 millimeter melanoma. The probability that the 35 year old is going to have a positive node is way higher than the probability than that the 80 year old is. So you're going to get an IGEP risk, a positive sentinel node for the 35 year old. That's going to say like 8% and you're going to be like, well, we should do it. And, and then you're going to get it for the 80 year old that's going to say 3%. You're going to say, oh, I guess we don't do it. I think what it's doing is actually like reminding us that old people don't like that they don't do as well with melanoma, but they're not that likely to have a positive sentinel node. Right. But maybe we could do that in a different way. Now what do we need? We need prospective trials. So we talked about the Merlin trial where they actually prospectively, you know, it's a different GEP test. They got the test on everybody, they blinded everybody to the result, then everybody got a sentinel node. And then they went back at the end and said, what percentage of people had a positive node who were low risk or high risk. Now that number was like 7%. It was between 5 and 10%. So it did not come out to a number that you're like, great, that's what I wanted. I can find the less than 5% risk group even for T1. It didn't. But we need a prospective study like that. They are doing side which is prospective, but it's not quite the same level of prospective as.
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A
Didn't Merlin just get added to the NCCN guidelines?
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B
MERLIN did just get added to the NCCN guidelines, which, I mean, I guess that you can put somebody into the discuss and consider. So if you were like, oh, look, you should get this, you know, oh, you know, it, it, it helps to put people in discuss and consider. I'm a little surprised that they got put into NCCN guidelines, but I think it's because there's actually prospective data in a trial done the way that, you know, they would want a trial to be done that made them put it in there. It. But again, it only, it only classifies them as discuss and consider.
- [23:54]
A
All right. And so for anybody who's not heard us talk about it before, the derms on drugs are big supporters of the NCCN guidelines. You can go, if you just go online and Google nccn, it stands for National Comprehensive Cancer Network and they have these amazing like flowcharts that are for, you know, what you're talking about Merkel cell or melanoma or like whatever that basically tell you what you know based on these character. Here's what you do there. It's very, very good and it's very data driven. You can be very certain that whatever recommendation.
- [24:29]
B
Second that. I always tell our, like every time I give like the melanoma lecture to the residents each year, I'm like, go on to nccn, make an account. It's free. NCCN guidelines get updated not infrequently, right. Like a few times a year often. So everything will be in there, whether it's a new immunotherapy option, a new study that shows you know when to use adjuvant therapy. They really incorporate these all into the guidelines. You might not always agree with it, but that is like your, you know, gold, your North Star and they are, you know, updated. There's a huge panel of experts that do it. So. Yes. And like, do I keep up with what to do with every stage of Merkel cell? Absolutely not. So NCCN guidelines, it's free. It's your best friend.
- [25:16]
C
Yep.
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A
All Right, let's move on.
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B
Pat, do you have any, any other insight into these papers?
- [25:23]
C
No. I mean, I, I, I think these tests are overused, and I, I literally never order them. I think they, they have utility, but it is in that multidisciplinary decision making. Hey, do we need to do this? And working with a multidisciplinary team in like a weekly cutaneous oncology, the oncologists and the surgeons never, ever, ever use Castle.
- [25:50]
A
So once in a while, I will
- [25:53]
B
say that they do. Here at unc, there is oncology. Oncology will occasionally say, you know, this would be helpful to have more information. So they do actually use it here. I think it's. I remember in Pittsburgh, it being minimally to never used and some people hating it. So I think it varies by center. But know what you're. I think that's part of it. Know what your surgical oncologist and medical oncologist will say or do before ordering it.
- [26:21]
A
Okay. All right, let's move on. Enough melanoma. Patton, what do you got?
- [26:26]
C
All right. My first six pack, which actually, it is more than a six pack, right? It's like what we tell the doctor. We would drink a six pack of beer, but it's actually like a 12 pack. That's. That's what our program is growing into. So my first not six pack. Papers from the February edition of Postgraduate Medical Journal titled, a retrospective study on Mohs Micrographic surgery combined with Adjuvant Radiotherapy in the treatment of Extra mammary Paget's disease analysis of 87 patients. So extra mammary Pagets. That's new. New topic. It was by Zhang et al. I had to do a little bit of reviewing with empd. It's been a while since I've actually seen a case. Maybe saw one a couple years ago. JAMA Oncology actually has a nice review published in 2022. Murad Alam was the senior author on that. So EMPD, epithelial malignant neoplasm occurs in apocrine rich skin, including the vulva, penis, and scrotum. It can be epidermal or invasive. Invasive EMPD should not be confused with secondary EMPD, which is EMPD that occurs with an underlying adenocarcinoma. EMPD is CK7 positive, CEA positive and is negative for P63, which differentiates it from SEC and Sox10. It is negative Sox10 differentiating it from melanoma. It can be CK20 positive or negative with CK20 positivity potentially suggesting secondary disease. But that's that's not a hundred percent. I. I actually emailed you guys really late, but there was this new algorithm published in December 2025. I'm just going to cover it really, really quickly at the end of my deep dive paper because that CK20 was like, okay, if CK20 positive, they have an underlying adenocarcinoma, right? That. That's secondary. But only like 50% of secondaries stained for CK20 positive. And like 22% of primary EMPD are CK20 positive. So it doesn't really help you really discriminate. Do they have an underlying malignancy or not? So all patients should be screened for malignancy. Age appropriate and location specific screening is recommended. Routine use of sentinel lymph node was not recommended, at least based on the review paper that I read. Surgery is the treatment of choice, and that can either be wide local excision or mohs. MOHS has lower rates of recurrence for non surgical candidates, which is not unusual sometimes. These are older patients and they're just not going to tolerate surgery. And it's going to be an extensive surgery. Wide excision would be required. So you can consider a miquimod CO2 laser, photodynamic therapy or radiation treatment, most often electron beam. All right, so that's my review. Listen to that five times. You'll ace any EMPD board questions.
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A
Wait, okay, guess what? So what did you come across? Like, what percent of EMPD has an underlying tumor? Is that like a. Like you're. You're good?
- [29:14]
C
18 in the. In the review. Okay. 18 of EMPD patients had an underlying malignancy. I am almost positive. Don't quote me on like a g.
- [29:24]
A
So like a GI malignancy, whatever kind of thing.
- [29:28]
C
Colorectal being the most common. It was really weird, the review paper. The second most common cancer associated with EMPD was breast, which that isn't that just Padgetts.
- [29:40]
A
That seems like it'd just be bad.
- [29:43]
C
So colorectal. And then you also think about bladder and urothelial and prostate and.
- [29:50]
A
Okay, this is. And this is fortunately something you're going to see so rare that the once in a while when you do see it, like you can go look it up and figure it out.
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B
Yep.
- [29:58]
C
Pull up that 2022 and pull up this 2025 paper that takes you through a staining algorithm. It's pretty sweet. It's probably too good to be true, but the numbers are pretty nice. All right, so the six pack article authors wanted to evaluate the effectiveness of combining MOHS with adjuvant Radiation. It was a retrospective review. 87 patients at Peking University First Hospital from 2012 to 2021. They still call it Peking University.
- [30:24]
B
I know call it Beijing, but that.
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C
That one stayed. Patients underwent Mohs and then once. What's that thing?
- [30:34]
B
Not just for ducks.
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C
It's correct. Yeah. Patients went Mohs and once patients were healed, they went underwent radiation therapy. Prior to 2015, they received electron beam and 3D conformational therapy. After 2015, they underwent intensity modulated ratiation therapy. I have no idea what the difference is between those two. And so. And I didn't bother to lear. No patient underwent gentle cure. So don't even think of trying that. People, Table 1 list patient and tumor characteristics. I don't want to get bogged down details. Most patients were men. Most tumors were in the perineum. Most tumors were dermal compared to epidermal. So invasive EMPD versus just epidermal empd. Three lesions were in the axilla. Like clearly that's an area where apocrine glands exist. But before I read this paper, I had no idea EMPD could be in the armpit. Did you guys know that?
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B
I've never seen it there.
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A
I mean, never seen vast numbers, but it makes. I knew that it was African rich. So I would have, you know, on a test, I would have gotten that right.
- [31:39]
B
That's what matters. As long as you got it right on a test, we won't have to worry.
- [31:42]
A
That's right.
- [31:43]
C
Yeah. Patient care. Let me tell you what, it's not my thing. Test patients are failing all sorts of therapies. All right? Median follow up, 71 months, 5 year local recurrence rate was 3.3%. So that's pretty good. Previous recurrence rates for EMPD were reported in 2023. 26.7 for wide local excision, 7.3 for Mohs. So just MOHS alone. So this went all the way down to 3%. So better. A fair number of patients had acute skin toxicities, but only 6 patients out of 87 discontinued therapy secondary to those toxicities. At the University of Pittsburgh, we, we talked about this just a little bit ago. We have a multidisciplinary tumor board which for cutane malignancies. And it's just awesome. Like it's an awesome tool for patients. And just you learn so much about skin cancers. And in my experience, when you ask the radiation oncologist, like, would you radiate this like 99 of the time, they're like, yeah, we can. So my sense is with empd, not unreasonable to Strongly consider adjuvant radiation therapy. And like everyone. If the patients can tolerate it, radiation therapy is not easy. 25 treatments. I think if it. They. They separated it. If it was a close margin versus a. There was a. Like, margins were greater than a centimeter. They actually changed the. The dosing and the fractionation. So it's. It's a lot. But if you took it from 7.3 down to 3, not unreasonable to consider. So get. Get your radiation oncologists involved in the carrier epin, EMPD patients, I think. What do you guys think?
- [33:26]
B
Yeah, no, I think so too. I thought that was interesting. That was good to see. They're tough.
- [33:32]
A
How many radiations did they give them? Like ballparky25.
- [33:37]
C
If it was like, if, you know, they met certain criteria on the margins, and if there was, like, close margins or the margins were positive, I think they took it up to 30. So 25 to 30. Okay.
- [33:48]
A
So a fair amount, but not like you're. It's not like you're going for a year.
- [33:52]
C
Okay.
- [33:55]
B
The mpd. Thank you.
- [33:57]
C
Yeah. Yeah. Well, something we haven't talked about and something. Of course, now we're going to see like one case in the next 10 years combined between the three of us. But, hey, we will be ready.
- [34:06]
A
There was that 2022 article in JAMA Oncology.
- [34:11]
B
Right.
- [34:12]
A
In the A.I.
- [34:13]
C
all right, so this algorithm. Cancers. The journal cancers 2025, December. They. The. The stain that I had never heard of was this TRPS1 stain. So basically, you get your EMPD patient and your first round of staining is CK7. CK20, TRPS1. If you are TRPS1 positive, that is primary EMPD. Like, that's it done. You're. You're done.
- [34:44]
A
You don't have to go looking for cancer.
- [34:47]
C
No.
- [34:48]
B
Wow.
- [34:48]
C
In this cohort of stuff, like, I couldn't believe it. That's. That's really.
- [34:52]
A
Never get an answer like that. We're like, hey, we got a new test, and it's useful.
- [34:56]
C
All right, if you are CK7 negative, which I didn't think was possible, but, like, 7% of EMPDS are actually negative for CK7. If you're CK7 negative, CK20 positive, TRPS1 negative colon, that's what you work them up for. If you're CK7 positive, 20 positive, TRPS1, then you do additional stainings. CDX2. If you're positive, you do another stain, SATB2. If that's positive colon. The diagram makes it much easier. And we'll put this in the slides.
- [35:32]
B
Yeah.
- [35:34]
C
And then if that CDX2 is negative, then you do P63, GATA 3 Europlakan and KX31 and that'll tell you the difference if it's urothelial, if it's prostatic or if it's primary perianal. So that T. RPS1 negative, you can still be primary, but it's more specific to the perianal skin.
- [36:01]
A
I want to, I'm, I'm going to isolate that clip and I. It's basically a foreign language like I was, I had no idea what you were. It was. But it's still pretty cool though.
- [36:13]
C
We will put, I will, I'll send you this little graph and when you combine that with my babbling, it'll be, it'll, it'll be slightly less coherent.
- [36:25]
A
All right.
- [36:26]
C
It's still going to be pretty co. Incoherent. Yeah.
- [36:28]
B
All right.
- [36:29]
A
So moving on. So for our listeners, I'm going to move on to it to a much lighter topic, much easier study to understand. So first one that I've got is spironolactone versus bicolutamide in female pattern hair loss. A randomized double blind controlled trial. So this was done in China and essentially they basically took 208, 204 women, 188 completed it. Randomized them to either 100 milligrams a day of spironolactone plus whatever else versus 50 milligrams of bicolutamide, whatever. I think they were monotherapy, but protolactone versus bicolutamide and followed them for 24 weeks using trichoscopy. And the bicolutamide kicked spironolactone's butt. So hair density, the frontal hair density was almost twice as good improvement. The improvement is almost twice as much. The hair shaft diameter, the frontal hair shaft diameter, almost twice as much improvement. Vertex dense, hair density more than twice as much improvement. Hair shaft diameter on the vertex about twice as much improvement. So the bicolute was a lot better. Now they, they did do like clinical photography at baselight in it at six months and in clinical photography you couldn't tell the difference, but that's probably just that they didn't give it long enough. So trichoscopy shows differences a lot faster than clinical. So my bet is that if they gave it like a full year and then took pictures again, you'd see a big difference. So now obviously I'm guessing that most people are like me and have not ever thought about the possibility of prescribing bicolutamide Turns out bicolutamide is a very cheap, very safe drug. It is. Well, it's pretty safe. So it's a selective androgen receptor antagonist with minimal cross reactivity. And the only real concern with it, about 10% of people will get mild transaminase elevations. Much smaller number, like in the 1% range, will get meaningful liver function, LFT abnormalities. And so if you do decide to use. So the first, the overall rate of adverse events was lower in the bicolutamide group compared to spironolactone. So spironolactone had more hypotension, edema, stuff like that. The bicolutamide, some menstrual changes, some rash, but overall, the biclutamate had a lower rate of adverse events. So as I did some digging into this, if you were going to prescribe this to someone instead of spironolactone, you would want to prescribe 50 milligrams once a day. And you would want to check LFTs at baseline and then monthly for four months, then every three months for a couple more times. And if they get through a year, you know, and their liver was fine, they're going to be like, you then can just check it once a year. But the risk of, like, clinically meaningful hepatic toxicity, super low. Like, super duper low. Like 20 reported cases. So, but that's in the setting of your monitoring it. So you're not just like, here's your drug. Go on your way. I thought this was very timely because last week was it. Last week we talked about the spironolactone in older women and older women.
- [40:08]
B
Yeah, I mean, yeah, older women. Women over 40, but. Yeah, over 45.
- [40:16]
C
They're older women. Women that are under 40, their lives.
- [40:19]
B
Yeah.
- [40:20]
A
So,
- [40:24]
B
yes. So that was. I thought this was really interesting. So bicolutamide, like that. So obviously this is also a drug like finasteride, you would not use in a woman of childbearing potential. Right.
- [40:38]
A
I mean, if. If they were. Yes. Okay. Yes. You said woman of childbearing potential, so. Yes, you would not. It'd be if. But if somebody. I would say if somebody had an IUD in, I'd probably be willing to prescribe this.
- [40:52]
B
Okay, so like Accutane. We'll think about it. Like Accutane.
- [40:55]
A
Yes, yes. At least like Accutane.
- [40:58]
B
Okay. And then this was developed to treat, like, bph, benign prostatic hyperplasia in men, or what was. What's the original use of bicolutamide?
- [41:07]
C
Do you know, metastatic prostate cancer.
- [41:10]
B
Prostate cancer. Okay.
- [41:12]
C
That's the tricky cell right there.
- [41:13]
B
Yeah.
- [41:14]
C
Normally, yeah, I usually treat metastatic prostate cancer, but for you, it's going to grow some hair, or at least your
- [41:23]
B
hair will look better under a microscope to people who are experts. But the average person walking down the street won't be able to talk.
- [41:31]
A
Well, at least not for six months every month.
- [41:34]
B
It'll be fine.
- [41:35]
A
And I can promise you won't get prostate cancer.
- [41:38]
B
Yes. Or if you do and it metastasizes, you'll do much better. Yeah, I mean, I think we need, like, the true clinical outcome data. Right. Like, they need something that is, like. Because none of us are treating our trichoscopic findings, we're treating. Does my hair look thinner or not?
- [41:57]
A
Yes, but it's strongly. The timing, like, six months was too early for pictures.
- [42:04]
B
And just. There's no such thing as topical bicolutamide.
- [42:08]
A
Not to my knowledge. But there probably will be after this.
- [42:10]
B
After this.
- [42:11]
A
Some compounding pharmacy is mixing it up right now.
- [42:14]
B
Yes, yes.
- [42:15]
A
And then you could also rub it on your metastatic prostate cancer.
- [42:19]
B
Ooh, yeah. All right. I like it.
- [42:21]
C
All right.
- [42:22]
A
Article number two. The effect of medication use on chronic pruritus in patients with type 2 diabetes mellitus. A multicenter cross sectional study. So basically, this was a study where they looked at this registry of people with chronic renal failure. I think they were actually all dialysis patients. And they looked at all the different drugs that they were on and saw if there was anything that correlated with being with chronic pruritus. And there definitely was. So the drugs that really mattered here. So, number one, alpha glucosidase inhibitors, which nobody's gonna be using any of those. You can forget about that. Number two, dipeptidiopeptidase 4 inhibitors had a relative risk of 1.29, so about 30% more likely. And then statins at a relative risk of 1.41. And they were additive. So if you were on two out of these three, your risk of itch went up even further. So this. Now, on the other hand, this was not a prospective study where they then, like, stopped the drugs to see, did your itching get better? Like maybe this was an association. Not a thing, but.
- [43:36]
C
Right.
- [43:36]
A
We know dipeptidiopeptidase inhibitors cause pemphigoid, so it kind of made some sense to me. And then statins, I know for sure make old people itchy. We've had that data for a long time. Because your skin has cholesterol in it, and your skin literally Makes cholesterol in the skin and a statin stops that. So statins do cause drier skin. So just a useful reminder, particularly those two drugs, dipeptidiopeptidase inhibitors and statins. And it also was my reminder that I to bring up again, I, I am a firm believer that we way over diagnose drug rashes. That if there's, if spongiosis is the primary clinical pattern, I think it's incredibly unlikely that something is a drug rash. There was a study on this a couple of years ago and basically it was common for people to get like temporarily better. Oh, we stopped the drug. Oh, a month later doing a lot better. And then a month after that they were, it came back again. The drug had nothing to do with it. But so spongiosis really takes me away from really thinking about a drug rash. Any lichenoid or interface, then I'm like all over like interface or lichenoid plus eos. That's a drug rash until proven otherwise. Otherwise, you know, morbiliform drug rashes dress, that kind of stuff are obvious. But for the non specific itchy old person with a rash, I think we overdo drug rashes in general.
- [45:01]
B
Or they, or we say, oh, that's a drug rash to statin and they stop their statin and they're better. But it's because it was really the pruritic component or. Right. That's not really an allergic reaction, it is an adverse effect. Right. Like I think that's maybe the way to think.
- [45:19]
A
That's a very good way to put. Right. Right. They basically made their skin so dry that they got itchy and then they could have gotten a rash and whatever from the scratching and the, you know, or the barrier impairment or that kind of stuff. All right, we want to thank everybody for joining us this week. We, we went through a lot, right. Got in some deep stuff with melanoma and gene expression profiling. We got into some stuff with extra memory Paget disease and a couple of little fun things. But you know, we, we hope you really learned a lot and we hope you laughed once or twice. But mostly we're hoping you're planning to join us next week. And until then, I'm Matt Zyrus.
- [45:54]
C
I'm Tim Patton.
- [45:55]
B
And I'm Laura Faris and we are derms on drugs.