Dermpedia Unknown Case Discussion with Dr. Artur Zembowicz (Dermpath & Soft Tissue Pathology)

Añadido: 2026-05-19

[00:00:08]Hi, this is uh Dr. Arthur Zamboitz.

[00:00:11][snorts] Uh welcome to the next Derpedia workshop. I'm here with Dr. uh Garrett Gardner who's joining me from where where are you?

[00:00:20]>> Danville, Pennsylvania.

[00:00:21]>> Oh, from Pennsylvania. Uh so um probably most of you know him uh especially from you know all of those who ever used the internet and typed in pathology or dermatology encounter on his uh content which is all over the uh the place and it's you know very high quality and I've always wanted to do workshop with uh Jarrett because I thought this would be a very good combination uh doing something uh together He brings the expertise in soft tissue tumors and he's one of those uh folks who are really very prominent in dermatopathology. All this alumni of Sharon Weiss is that correct you must have been one of the last maybe or to >> yeah let's see there were there were about four or maybe five more people after me that that trained before she retired but yeah real great great honor to get to work with her for a year. She was amazing.

[00:01:19]>> So so yeah there was something amazing about her. I never met her in person, but I think the impact she had both in terms of her writings uh but also the impact she had on people who u you know did fellowship with her and what they accomplished >> later on in their lives. I think that's amazing.

[00:01:42]So yeah, I'm glad uh we are here together. Um you folks, you know what to do. So, I'm asking everybody to scan the QR code which is here to join the mantimeter presentation and I'm going to put the uh link to the menntimeter presentation in chat for those of you who want to use your uh desktops. My recommendation always is to use the cell phone. It's more convenient. Um you can also go to ww.menty.com and use the code that's on the screen to join the presentation. That's another way to do it.

[00:02:22]So I Let's start with a menntimeter training question. So for you guys on the menntimeter, uh tell me what best describes you.

[00:02:32]Um and you will have a slider and you slide to the left if it's you, to the right if it's not you. Okay.

[00:02:48]Okay. And I give you 10 more seconds.

[00:02:54]And in the meantime, you know, those of you who are still joining, here's the QR code uh to scan on your cell phone if you want to participate actively. And we'll be asking a lot of questions today.

[00:03:08]Okay. So that's uh uh here is the here's our breakdown of the first mantimeter question. Uh so so we you know usually have experienced people on this calls and here is the second question. How many Duredia events videos have you participated or watched so far?

[00:03:38]And I'm encouraging everybody to scan the QR code and join the act join actively and I give you 10 more seconds.

[00:03:47]>> Just for anyone out there who voted uh I find Squamish solution don't don't find you know if you find squam solutions difficult I still do. I've been in practice [laughter] for a few years from almost every day. That's a leftover from from uh last workshop that I did with u um with Christina Co from Yale.

[00:04:08]>> Oh yeah, she's so great. I love Christine. She's amazing.

[00:04:11]>> Yes. Yes, that was was fun. So >> yeah, you'd think it should be so bread and butter and easy and yet here I am struggling over a decade into practice and I'm sure I still will be at two decades.

[00:04:20]>> Yes. So welcome especially for those who were for whom this is the first time and here's the you know second uh next question. How many Dr. corners events or videos have you participated what so far and I expect that actually this will be higher number let's see that's not a competition you know it's just I was just I was just curious >> I won't be offended if you all say zero it's fine >> huh no uh oh so you have more f first timers >> awesome And well that's a Darpedia audience. So it's kind of a similar breakdown I think.

[00:05:01]>> Well, some people did over a hundred.

[00:05:03]Wow, you guys are That's amazing. One we got one person over 100.

[00:05:06]>> Oh yes.

[00:05:07]>> Bravo. That's amazing.

[00:05:09]>> Yes.

[00:05:09]>> If you can tolerate me for that many videos, that's that's impressive.

[00:05:12]>> No, we have quite a few. Yeah. And uh and this estimate. So um we certainly have over you know overlapping audiences. That's that's that's for sure. Um so the next uh oh it's time to do some work and uh look at some cases and let me start. So um uh just yeah you why don't you start and tell us about this case and we'll look at the slides.

[00:05:45]>> All right. Yeah. So this was a a young girl 5 years old. She had a kind of slightly uh soft scalp mass present since birth and clinically they thought it was a vascular lesion. I think they had even if I recall correctly done ultrasound. It looked cystic and and probably vascular. So I think just uh kind of because it was you know it was noticeable. I think they decided to remove it mainly for you know cosmetic purposes or just so there wouldn't be a lump there anymore. And uh and then we uh got the pathology results. Okay.

[00:06:17]>> Slides here.

[00:06:20]So here is that uh excision and there were actually two I think right or >> there I think this is just one I think there must have been a little cut in the the top of it like it it opened up u at some point during the operation maybe that that I don't think is a real ulcer I think it was a kind of a defect but >> but it was a complete excision done by a pediatric uh surgeon I believe or plastics one of those >> and they you know They took it all the way down to the the fat and kind of took it off the the galia off the top.

[00:06:53]>> So what I'm see I see a little hemorrhage in the center and we I see there's kind of like a spaces.

[00:06:58]>> Yeah.

[00:06:58]>> The periphery and uh so let's show it to the audience.

[00:07:05]Uh so here's the high magn higher magnification on those spaces that are lined by cellular by cells and there's a blood inside.

[00:07:34]So I just want to show you kind of a sample of what might be. So that's the lesion.

[00:07:41]That's >> and then at the periphery you can see it kind of uh trickles out. It's not like very well circumscribed >> um either towards the bottom or the sides. It kind of, you know, trickles in between normal structures >> and that some vascular >> proliferation too. Or maybe that's kind of something that looks like blood vessel. And here's the blood vessel that you mentioned that it was apparently in the surgical report there was a connection to a blood vessel. That's right. At least that was how it was reported. So let's do let's ask the audience what you know do you have a diagnosis even just based on what we've shown which would not reflect probably the real life situation but what are the considerations so if you have those considerations you could write it uh in on the mentimeter and in the meantime I'll show a little bit more of of at H& So we have a young child with those spaces filled with blood.

[00:09:06]Okay.

[00:09:08]So, let's go back to the mantimeter.

[00:09:13]>> Those are all great ideas.

[00:09:14]>> Yes. So, that's you know vascular mar formation you know the the more responses are from the of the same >> Oh, right. They get larger if they get larger more people vote for it.

[00:09:25]>> Yes. Yes. So, okay.

[00:09:28]Um I I think that might be enough on for this. And now that question for you is which of the following stamps would you like to order? Are there any other considerations um that you might have? And this should be a quick I give you 20 seconds to respond.

[00:10:04]Okay.

[00:10:07]So, you know, vascular markers, you know, a few votes for AMA, CD34, keratins, and some other options were selected.

[00:10:16]So, let's take a look at some of those.

[00:10:18]Uh D240 stain.

[00:10:27]So Jared, narrate and walk me through this one.

[00:10:32]>> Yeah. So do you want me to to talk about like what I was thinking and how how I was approaching this and then >> let's let's let's just analyze the uh slide and then >> Yeah. So I mean here's D2 just report and then we'll have a discussion because we positive right around >> very nice staining um control you can look up and see there's lymphatics in the dermis it also stains some of the outer root sheath cells so it's always nice to know what internal controls will light up you know >> so all these spaces are positive for for D2 pretty much okay >> uh another It was popular and here it is.

[00:11:23]And and that looks negative. Ouch. Yeah.

[00:11:27]Dead negative.

[00:11:28]>> That negative.

[00:11:31]And the next and I also did a 34 and 31.

[00:11:36]And 34 was cleanly negative. and 31 there was like a little bit of wishy-washy staining here and there probably histioytes but mostly negative so >> and you thought of something and you are and like a few members of the audience you did EMA that you want that you chose to share and let's show what that this one showed and look uh just as a little bonus look at how tiny those sebaceous glands are because she's a kid right the sebaceous glands are so little in children and very immature until puberty, right? When they get androgen, you know, you know, response and they get larger.

[00:12:13]>> So, that's kind of cute and it's a nice internal control.

[00:12:17]>> And yeah, look at that EMA. It's not not diffusely positive, but certainly there are areas that are strongly positive, especially towards the the deep aspect of the lesion. And uh over towards I think the left side of the slide a little at the bottom there's an area kind of by that sclerotic zone there's a little area where you can see kind of some slightly round kind of uh world structures that are EMA positive.

[00:12:41]>> It's pretty nice.

[00:12:43]>> Yeah. So it is positive. So now what is your diagnosis? That's a question for the audience. and 5-year-old scalp leion.

[00:13:17]Yeah, I love this case, too. whoever gave that heart. I This is like a really really awesome case that I'm easily excited about cases and one of my former fellows who's now my my partner Michelle Pitch, she she always she accuses me of saying every case that I'm like this is the best ever. And it's true. I say this is the best ever all the time. So we have a joke she'll be like is it TBE? Is it the best ever? And I'm like let me show you. And she's like okay that is the best ever.

[00:13:42]>> Oh you're next.

[00:13:43]>> I like that she kind of pokes fun at me but she's totally right. I'm easily excited but this case is the best ever.

[00:13:47]Yeah, that's that's what Dr. Mim he was like because I I I was very lucky to work with him for 10 years. So >> Oh, that's so cool.

[00:13:55]>> And he was always 100% on [laughter] just nothing in between.

[00:13:59]>> I I'm so glad I got the chance to meet him at a meeting at UCAP one year. I got to meet him and went up and shook his hand, said hi. And I'm so happy that I had that experience. But I've heard just so many great things about him.

[00:14:08]>> Yeah. So, so there are, you know, there's like a competition between, you know, hema and menoma um in and lymphenoma um and you did a few additional stains that that uh included those and so now would be good time to to say what was your thought process and uh >> yeah so I >> how did you arrive at the diagnosis and your diagnosis was >> this is a maningthelial hamaroma uh which some people also use the term ectopic meningioma or cutaneous menioma although it's really probably in this context in kids when it's congenital it's not neoplastic actually it's probably a m kind of a a malformed uh hammerous process maybe a bit that got left behind embryologically you know which I think fits with that idea that they had that kind of cord they thought it was a vessel surgically but I think it was kind of a tether of a little bit of tissue that connected uh probably originally to the the dura you know um and since there was no defect in the skull I call this like a mining mileil or a mininga seal anything like that but it's kind of you could think of it as being within that same spectrum I guess so um uh yeah so what I and and some people have called these I think in when they call them cutaneous meniomas people have divided them into three subtypes type one which I believe is like this form which is really a hamaroma and then there are actual meniomas like neoplastic uh that can arise outside of the skull or that can grow through the skull uh pretty rare but I have seen that happen for so in this case it looks like a vascular lesion right so the problem in fact one of my partners got the case first and they brought it to me and they said I think it's a heangioma but it's I'm not exactly sure is there a special name for it and so that was my problem and that was the first clue that that this was something weird was it looks vascular but it doesn't fit neatly into a box for a 5-year-old kid there's not a I was thinking what are the options we have well there's infantile hemangioma right the kind that that babies get the strawberry heangiomas that kind of regress over time. Those look very different from this, right?

[00:16:09]They have little tiny vessels packed really closely together. They're very cellular. The old name for those was cellular hamarts. I'm sorry. Um cellular hemangi of infancy. So, this is definitely not that it doesn't and and if you did glute, guess what? Glute one would be positive here probably. And I would normally have done it, but we happen to have been out of glute and we're waiting. It's on back order. We're waiting for a new uh stain when this was happening. So uh that's why I didn't have a glute for you here. But normally glute one would be a nice stain for this too. So that could confuse you. If you did glute, you would say, "Oh, it's infantile hemangioma." But in fact, uh meningothelial cells are glut one positive too, just like perinurial cells are. So So I looked at it and I thought, well, it's not infantile heangi. Then could it be rich or niche? Like congenital hemangiomas, the rapid involuted kind and the non-involuting.

[00:16:57]The rapid involuting kind would be gone by 5 years old mostly. And so that wouldn't fit. And then the non-involutin kind, the ones I've seen, they're much more well-formed channels. This is actually pretty infiltrative if you think about it. Look what it's doing.

[00:17:10]It's individual cells that look kind of like endthelial cells wrapping around individual discrete dermal collagen bundles wrapping around normal vessels almost like the promontory sign of capacity saroma. In fact, I actually even did an HHV8 stain here just to be totally safe because there are like lympangioma like and and cystic kind of variants of capacy. I've never encountered one in practice, but I've seen them in study sets. So, it would be really really rare for a 5-year-old to have capacity saroma, but I thought let's just be totally sure. So um I the best thought I had was that maybe this is either a weird vascular malf for a lymphatic malf for like a so-called lympangioma because sometimes malf formations can get pretty infiltrative and kind of mimic that growth pattern of capacity or angio saroma. Clearly in the scalp of a 5-year-old there's like just no way this could be an angio saroma.

[00:18:01]It's exquisitly rare for angiocaroma to be in kids. I've never seen a case in a child and and if they were I mean there's no atypia here. It's very bland.

[00:18:09]So as I looked around I also thought about you know there is this thing called mining hemorrhoma and they look kind of lymphioma like or vascular they have cystic spaces they don't really look at all like the actual tumor menioma and as I looked around and thought about that I encountered a few simoma bodies which uh Dr. resemble which just showed down there. There are a few simomatous calcifications at the base of the lesion right there. And there's also a few areas where the cells are a little more round and they're kind of vaguely whirling and swirling within this dense collagen stroma. Kind of like the whirling and swirling you would see in a a mining or a perinary. So I I my initial round of stains I think I did uh D240 CD34 CD31 and I for I usually like to do URGK but for some reason I forgot to order URGK. So D240 came back beautifully positive and I forgot about the fact that guess what miningthelial cells and miningomas are usually D240 positive. So that's another trick. So once I did the URG URG was completely negative and so was CD34 and 31 was mostly negative. So URG in my hands, in my experience, is 100% sensitive for vascular and lymphatic tumors and proliferations. Now, no stain's perfect.

[00:19:22]I'm sure if I do this long enough, eventually I'll be proven wrong. But basically, if it's URG negative, the chance of it being a vascular or lymphatic proliferation is close to zero. I'll say that. I've in my experience, I've never yet seen a vascular lesion or lymphatic lesion that's negative for URG. Um, so uh it's a really it's not specific marker, but it's very sensitive. So the fact that this was totally negative for URG basically takes lympangioma, lymphatic malfform, vascular malfform, all of that out. Um and then then I had the thought of like well what other things could I do if I really wanted to prove these are miningial cells and I had to do a little bit more searching to find out you know what other things stain mining cells but wouldn't stain vascular and and I that's when I had discovered another thing that was positive is ecadherin. Um, I found a paper that that was talking about meniomas are often positive both for D240 and for ECADherin and I I don't have the slide. I didn't upload it. I these are pretty big files and I didn't want to upload a million of them. So, um, I did that and I did a couple other markers PR progesterone receptor which is positive in meningiomas but I wasn't sure how much staining it would have in like normal mining cells. It was kind of patchy focal positive for PR. A decent bit of SSTR2 which is sematastatin receptor 2. That's a positive marker in mining cells and mining and then ecatherin was nicely positive. So all of those things together supported that this was miningthelial origin. I didn't find any gal tissue. In fact, I think I even did a GFAP on one block to make sure there was no gal stuff in.

[00:20:49]>> There's no chance whatsoever. This is probably the most the worked up meningo hemorrhedly. I did a few for teaching because it's just such a nice example, you know. Um, but I thought it was very lovely and it and when I was looking back in the literature back in the 1990s when this was originally described, it was noted that these tumors can have a growth pattern that mimics angio saroma.

[00:21:12]And and of course in a 5-year-old, you wouldn't really be worried about that.

[00:21:15]But some of the cases originally described were congenital lesions but that were present until adulthood. And so they were removed in adults and then you could that kind of growth pattern.

[00:21:23]If this was an old sun damaged person, I'd be worried about angio saroma even though there's no atypia. It would concern me, you know, to see it grow like that. So such a cool amazing case and someone said why not an atreetic maninga. I I think arguably you could make the argument that maybe these exist on a spectrum with that. I mean >> this is a clinical pathological entity.

[00:21:42]You know for me the nuclei I mean you just want to see the this nuclei. These are many you know very fine kind of salt and pepper type of nuclei. They're very characteristic >> for this entity. And actually you know pediatric dermatologists are very familiar with this entity clinically because they present as an a bald patch and they're not the differential of a bald patch in a child is very narrow and and here the head the hairs they stick out like an uh around this uh kind of almost like horizontally there's like a corona. So there's very characteristic clinical appearance on >> yeah unfortunately there was no clinical photograph for this. really wish there would have been. That would have been cool.

[00:22:25]>> Yeah. Wonderful. I think that was that's a >> And it's such a big one. I've only seen this one other time in my career. It was I think on the nose of like a 10-year-old and it was really tiny. I think it was on the nose, which was kind of weird, I thought, but uh it was a really small lesion, the only other one I've seen. So, this is a really nice, beautiful example.

[00:22:45]>> Wonderful. That's uh really great. Let's see if there are any questions.

[00:22:49]>> Thank you. Whoever say I had Mu Dwan uh you come up with nice cases. I try my best. The cases just find me is what it what it seems like.

[00:22:57]>> Yeah, it's it's really great. you know, you have a different style and different uh you know, I I'm intrigued by controversies and by by things that are um kind of not clear-cut and that's a lot of content that I share, which is good for experienced people on different perspectives and but you you have this nag of of describing this, you know, lesions and all this differential diagnosis. And >> my favorite thing is like the rare really perfect example. I love those and the controversy I find is like it is interesting but it's also challenging and present I don't always know exactly the right answer and I I' I've kind of shy away sometimes from making videos about that stuff because it's a lot harder and more difficult to make a video about >> yes >> it requires much more preparation so kudos to you Arur for doing >> well it's my it's more of our personality and kind of what what what drives us you know uh but but you know that's that's really fantastic um piece of education.

[00:23:57]Actually, I you know, one wonder.

[00:23:59]>> Yeah, I learned a lot from that case because I had to like delve into like thinking about stain. I don't think about meningthelial stains very often and it was really fun to to do a little searching on that.

[00:24:08]>> Okay, wonderful. Case two, a 23-year-old female and any story at this point and we're going to show H&M's plaque on the lower.

[00:24:20]I can't remember how they they said there was a clinical photo, but no one ever sent it to me and it was it was an outside consult case in the past. I I try not to take consults anymore because I like to go home and see my family. But um uh but yeah, they they just said it was a kind of a reddish uh vi, you know, reddish uh plaque on the the leg of a young woman. I think I've been there for a few years, slowly growing >> if I recall.

[00:24:44]So, you know, that's kind of a busy case, busy >> lesion, busy tumor, nothing in the dermis. Yeah.

[00:24:55]And >> this one really >> vascular, doesn't it?

[00:25:04]>> Yes, it does. This one really gave me a hard time and we finally figured it out with the help of a fellow actually.

[00:25:10]>> Yeah. Let's let's let's let's kind of digest it. that's presented and kind of goes deep into subcutaneous tissue a little bit patch inflammation kind of bland nuclei but kind of >> agree >> bubbly and here we're infiltrating fat the tumor infiltrates The fat again has those nuclear bubbles kind of. Okay, so that might be it for H& to get us started very infiltrating in the periphery and then um we're going to show some H& actually imunostochemical stains before we ask about the diagnosis because you know I'm sure all of us would you know have a panel uh to assess a legion like that and let's look at those three that you picked to share.

[00:26:23]CD CD34.

[00:26:35]It looked positive as the vascular leion would but are the vessels that are staining or >> Yeah. And I did a 30 there was a 31 also but unfortunately the slide was um it came with the case. It was broken and so I I wasn't able to get a scan of it because of that and it was very >> positive, right? There's no Yeah. I mean, there's no no >> 31 was like the similar pattern but a little cleaner looking, you know, as is usually the case with 31 >> smooth muscle actin.

[00:27:05]Let's look at that one.

[00:27:14]So we see vessels but fewer vessels or vascular structures than than on the H& that are positive. Right. Right. There's some cellularity in between those vessels. Let's go into the subcutaneous tissue where that infiltration occurred.

[00:27:39]So these are nuclear of those cells that we we so we'll have to come back to the H& also was kind to share the S100 stain and this one I did not do at first. This was a a kind of afterthought that came later. Um uh once the >> once I thought about things a little more and had some extra >> once you had a dead alley.

[00:28:11]>> Yes. [laughter] >> So it's positive, right? So there's there's a staining and and and those cells look kind of more kind of dendritic in a way. So let's take a look at the H& one more look and then we'll be I think at the mentimeter soliciting suggestions about this lesion and here actually before that I added one more thing for you to consider. How about a blend because we have a blend spin cell tumor with expression of CD34 and S100 but negative for sock stain and we don't see have that stain but I added it and now what is your diagnosis?

[00:29:13]So Jared, what else would you tell us kind of about your processes? people are on the mantimeter typing in >> well I don't >> this vascular analogy I think that that is something >> kind of >> yeah so that I had trouble with um >> I ran out of time I there are a couple of h& on this excision and uh one of the other ones really looked very much vascular like the dermal component and and the subq part was only on this slide so I wanted the the other slide was actually what I looked at first that just had these really prominent kind of infiltrative but bland thin compressed dermal vessels that trickle between the collagen bundles, you know. So, when you see that, when you see, you know, thin but well-formed, bland vessels that that trickle between collagen, you know, that that reminds me of something. I've not seen anyone type it out yet. So, see, I I think maybe I just made a diagnostic uh an initial error and I couldn't let go of it, which is is kind of the point of why I wanted to share this case. It's an interesting and and kind of uncommon thing, but also it was an example of like how I I made a mistake at first and it caused me trouble >> uh because of that mistake. So, >> yeah. So, let's see what people >> Yeah. Let's see what you guys think and then I'll tell you what I was thinking.

[00:30:32]Yes, that's exactly what I thought and thank you. You all made me feel better.

[00:30:35]My first thought was this looks like a microular hemangi kind of but it's weird. It's not quite right. It's so big. It's so deep. There's all these extra cells in between like that look like histtoytes. It's going into the fat. What in there? Lymphosytes scattered in there. What is going on?

[00:30:51]Like I've never se I've not seen that many microangular hemangias. They're in my hands at least or in my experience pretty uncommon. I've I've seen I don't know a handful of them in my career. So I thought this that's the closest thing I could fit it to. But I was like but it's not right. So kind of like the first case looks maybe like a weird vascular thing but it doesn't fit neatly into a box. And you know, sometimes things are like that. They don't fit into a box. So my main question then is, is this something that is uh a normal desri a described entity that's just a weird variation of it that I've not seen before, a different flavor of a of a of a known entity? Or is this some unclassifiable unknown entity, you know, that just has not been reported yet? Or is this something else and I'm being tricked? And in this case, it was something else and I'm being tricked. So I I thought this is probably weird microvenar hemangioma. the outside pathologist had thought the same thing and I I looked at their workup and before I saw that's what they thought I thought the same thing. I kind of came to the same conclusion as them but like them they they said but it's kind of weird because of how deep it is how infiltrative how cellular and I felt the same exact concern like it's not quite right. It looks benign, but I I generally I prefer if possible when I have a weird a tumor that looks benign, I like to have a name for it if possible. And that's because one of the the lessons my mentor Jay Row at uh at Houston Methodist Hospital who passed away a couple years ago, but really one of my greatest mentors, the reason more than anyone else that I became an educator is because of Dr. Row. And Dr. Ro always said if there is a tumor that's a a neoplasm that looks benign but you don't have a name for it you don't know what it is don't just call it benign neoplasm no unless you're an expert in the field or you show an expert and I think that's good advice because that's the way you make mistakes right think about DFSP or or a lot of other soft tissue tumors they don't really cytoologically look malignant right many of the transllocation sarcomomas don't look malignant uh and yet they're malignant because of the pattern so that's the kind of thing if you don't know about that pattern you can get into trouble And I don't know, I guess I'm maybe approaching expert level, but I still don't feel Dr. Weiss told me, referring back to Sharon Weiss, she said, "Jared, do you know what the definition of an expert is?" And I uh we talked a lot about other things besides pathology. And you know, some people say an expert is someone with 10,000 hours of experience, which I I think I've got my 10,000 hours now. But I love the the practical way she said. She said, "Jared, an expert is someone who can look at the slide and instantly know whether or not they will be able to solve the case." And I love that. And Dr. wife could do that. You know, she would either know this is something unclassifiable or this is X, Y, or Z and I know what stain or what work up to do to get there. I still don't have that complete confidence. I'm always like, this must be a thing and I just don't know what it is. And then I'll send it to an outside expert and they'll be like, yeah, we're not sure what it is either. And that's that makes me feel better, but it also is unsatisfying. I want the answer, right? So, I I still don't have that total confidence that I'll that I'll not missing something. So anyway, >> so another just let me interject.

[00:33:49]Another definition of >> of um expert is access to microphone >> in some circles. That's that's what >> true. Whoever's the loudest voice is the expert, right?

[00:34:02]>> Access to microphone. So here's the question. Which molecular test would you like to perform?

[00:34:07]>> And I saw some people on there thought of it. Very good.

[00:34:10]>> Yeah. So let me give you 20 seconds.

[00:34:15]So the thing is is Dr. Zimboich helps us here by showing the S100 and bringing up that really great point of co-expression of 34 and S100 without socks 10 expression. That is a distinct and unusual combo of stains that right away should make you think of what you guys thought of an Entre rearranged neoplasm.

[00:34:35]But that was not on my radar at all. And I do know a bit a little bit about that tumor. I've I've actually diagnosed it before multiple times. I've made a video about it before. It did not occur to me here at all. And I'll tell you what really helped. It was humbling and also awesome. I had a I hope she doesn't mind, but I'm going to call her out by name. I had a visiting fellow from from Penn State Hershey, uh, Dr. Sydney Hoskins, who was who was working with me for a week, uh, because they don't have as much soft tissue at Hershey. So, she came and visited for a week and and spent time with me. And I was showing her and said, "Oh, this is weird vascular lesion and and you know, I think it's kind of like microangular hemangi, but it's not quite right." and she was like, "Well, I didn't really really realize that it was a vascular lesion at first. I I thought it was some other spindle cell lesion that just had vessels." And it was really that like fresh set of eyes uh that was so helpful because I was like, you know, maybe maybe it's not a vascular lesion. And the more I looked at it, the more I realized there are areas with lots of extra cells and maybe that's the reason there's extra cells in between the vessels is because those cells are actually the leional cell and the vessels are just like a bonus, right?

[00:35:38]They're just a really rich vascular network. And there's a tendency sometimes for pathologists to fixate on vessels and think something's a vascular tumor when it's not. And I I often like to teach about that and I fell right into that trap. And this is a good example of like anchoring bias, right? I thought of microar heangioma and I couldn't let it go. And so I ended up doing an NGS fusion panel on this and I even felt kind of silly doing it because the outside pathologist was like, well, could this be a heangioendotheloma or something? And I was like, no, it doesn't fit into any of the hemangiotheloma categories. And you can't just call stuff himtheloma NOS or else you're just making it a waste basket. But I the reason I did the panel is I thought I don't know exactly what this is. I want to make sure there's not not something else I'm not thinking of.

[00:36:20]And it is it was a big excision they did but it was still positive at the margins. So the question was going to be do they need to excise it more or not.

[00:36:27]And even though I thought it was benign, I didn't have a great name. And I'm so thankful I did that panel because it came back with an NRE 3 fusion. And it was while we were waiting for that that I shared the case with Dr. Hoskins and she said, you know, I didn't really think it was vascular at first glance and she was totally right. And that's when I thought after I I did the S100 later and it was positive and I was like, oh, it is going to be an entrefused neoplasm and that's what the molecular came back as. So, um, these are a new emerging class of tumors.

[00:36:56]Entre fusions are in a lot of different things, right? We know spitzoid lesions can have them. Uh, infantile fibers saroma, which is a really rare soft tissue tumor in babies. um these and then this nebulous group of entre rearranged misinkal neoplasms. So this is I imagine this because it's an emerging thing over time the new WHO's will probably eventually parse this out into more than one thing I suspect because the question is well what are they what do they do well it's not really clear what the WHO currently says is basic when we're asking about behavior of these if they look benign they will probably have indolent benign behavior if they look malignant and have an intro fusion they'll probably behave like a saroma so so it's it's maybe not exactly one lesion but kind of a group of misenal tumors that have entre fusions that have a variety of different behaviors depending on how the individual case looks and they have a wide wide range of morphologic features.

[00:37:51]So I have another case on my Kiko um in my Kiko mega index for soft tissue. If you go look up Entre, it was a case I presented in France a few years ago at the the AP meeting and it had in the same tumor had areas that looked like DFSP, areas that looked like dermatop fibram, areas that infiltrated fat, areas that had facasicles, areas that were bland, areas that had pleomorphism, all in the same tumor and it co-expressed CD34 and S100. So yeah, weird spindly tumor that you can't quite put into a box. Keep this one in mind because it can really have a range of features and can mimic a lot of other stuff. So some of these originally were called like lipop fibromyitosis like neural neoplasm, but then people realized they were S100 negative, so they weren't really neural. They can look kind of like neurop fibram sometimes. This case did not. I'd never seen one with such a robust rich vascular network as this case, and it really tricked me. But if you look in the subcutis you can tell that's not a vascular leion there, right? there really are more spindle cells, but I just couldn't let go of how my initial impression was microular hemangioma. So, it was a it was a nice uh thing. And someone asked about pantrek. I don't have the pantrek stain in my lab. And and from my reading about pantrek, it's a stain that can work, but it's a lot of times if you do pantrek, you still often end up needing to follow up with molecular because it's it doesn't identify all trek fusions and then it's not and it can sometimes stain things that are not actually rearranged. So it's a kind of a you know some of these u uh imunostain that are surrogates for molecular are really really good and very specific and some are not and my reading about pantrek has been that it's it's not as good as some of the other ones at least so I think it's probably helpful for screening if you have it but I don't have it available to me currently >> so I just went to the molecular >> one point I would make is just looking at this h& is there's certain monotony >> of the cells and that is always a kind of a clue about possible uh fusion associated neoplasm you know in any context melitics of tissue >> that's right >> and um you know ju just a clue and you know I'm very fortunate that I have access uh to NGS and I usually just go to NGS and it's >> I love it the more I've used it the more I'm finding stuff and it's it's helped me quite a few times.

[00:40:08]>> Yes. So, in this case, let me think. I I can't remember. I think I actually I copied my report the other day and see I'm trying to think what did I tell them.

[00:40:19]>> Yeah, I think we should go watch you know Jared, you know, I think >> the next case. Um oh actually a little plug for the D upcoming Duredia course which is going to be held in April 15th through 17th and change from the last couple years where we were only virtual it's going to be an inerson component in Boston. So, you want to come to Boston, have some nice um you know, experience Boston. And this is actually a very good time because next weekend it's the that's when the Boston Marathon >> uh uh is and this is also the weekend where we celebrate um you know the first battle of the American Revolution in Lexington. So if you want to go to see in the reenactment of battle of Lexington on Concord >> and what a what a stellar lineup of speakers too.

[00:41:13]>> Yes. Yes. It's going to be great and we will be you know talking about interface of um you know the the subjects kind of between dermatop pathology and general surgical pathology including like mucosal pathology of talmic pathology gyn you know pathology lymphas melitic lesions and squamus lesions. So, it's going to be >> That sounds awesome.

[00:41:36]>> Good.

[00:41:38]Okay. Next case.

[00:41:41]Case number three. 67year-old Jared. Why don't you take over?

[00:41:45]>> All right. Yes. So, this was an older adult uh woman and she had a mass on the the foot uh that podiatry uh removed by excising. MRI had been done ahead of time. found that it was well circumscribed in the forefoot about 2.5 cm and between the first and second metatarsal head. Um so podiatry did a complete excision and and it was sent to pathology.

[00:42:11]Okay.

[00:42:16]very kind of a circumscribed lesion with a huge like a capsule looks like or a lot of pigment. So much kind of pixelating a little bit slowly or maybe it's out of focus skin. Maybe the skin is out of focus or it's pixelated.

[00:42:46]>> I think it was in focus. It must just be loading.

[00:42:49]>> Loading. Yeah, >> cuz I checked it ahead of time and so it should come in.

[00:43:04]Let me see if there's there's another slide.

[00:43:08]See, let's see how that one load. It looks like the website is a little bit on the slow side here.

[00:43:20]Oh, here we go. I think we're just starting getting a sense of cytology.

[00:43:30]It's always hard to see cytology in the context of hemocitarine and because then you know nuclear from he nuclear from the tumor or the nuclear from the macrofasages.

[00:43:45]Yeah, agree. And especially on that other slide, um at first everything you see is just pigment and fibrosis and reactive change and a bigistic blood fil and fibbrin fil space.

[00:43:57]>> Um >> so a slide like this uh you know I my initial impression might be a little different than and it was once I saw the next slide that the one that our tour showed first that I was like oh wait a second.

[00:44:11]>> Yeah it's kind of interesting. Low power, right? The cystic hemorrhagic.

[00:44:19]Does anyone know what the yellow stuff is?

[00:44:22]It's not ink.

[00:44:25]There's brown kind of granular pigment in there, but there's also bright yellow stuff being deposited in the tissue.

[00:44:33]>> Very good.

[00:44:37]>> Something we don't see very often in derm path. uh because uh hematid and so I had to look it up again because I always forget the the mechanism behind it but it's what happens when blood uh when when he breaks down in low oxygen environments. So I actually found a paper I was trying to remember what the pathway it's that urethraittes break down and pferins are released from hemoglobin and then those convert to belly veritin which becomes crystallin hematidin. So they make like these little crystals. Sometimes they even polarize, sometimes they don't, I found.

[00:45:06]But uh you you I see it in deep soft tissue more and and rarely in skin because you just don't often get blood filled pockets in the skin that are low oxygen, you know, but I see it like in ceroma cavities, old hematas and here there's clearly been a lot of bleeding, right?

[00:45:20]>> Yeah.

[00:45:22]>> So you offered additional information that this lesion was positive for Desm.

[00:45:26]And so those the cellular areas EMA a few cells and alk1 and then the next step is a question about your diagnosis. Yeah. So let's let's see what people think while I'm still showing more of that lesion.

[00:45:52]That's inflammation at the periphery. M >> indeed lymphosytes and plasma cells mostly if I recall.

[00:46:04]>> Yeah. Yeah, that's exactly what it is.

[00:46:06]So let's go back to the mentimeter and load maybe 10 seconds.

[00:46:13]I mean uh to see what people think.

[00:46:21]So it looks like people like angatoid fibro fibrosisty for the diagnosis and you had information about uh the NGS and we don't have to run it again because it looks like people got it on H& right >> very nice >> and gumatoid fibrosis.

[00:46:47]Yes. So, so this is a tumor I've I've been fascinated with for a long time because it's just so weird. It it's like sheets of these hyocytoid cells usually with a blood filled cystic space in the middle and then usually with a peripheral pseudo capsule and a variable amount of of inflammation lymphosytes and plasma cells. Usually, sometimes it the inflammation can be so rich that it looks like a lymph node with a a nodule of sensitial tumor in the middle of it.

[00:47:17]So, I've got an example of that on Kiko, a really nice one that mimics a lymph node. So, this case is weird for several reasons. Okay, so this is a tumor that's good to know about because it's so weird and it can look kind of different every time you see it. Each one I've seen has like a little bit of a different flavor, but they the blood can confuse you because when it when there's a lot of blood and when there's pigment, you can get thinking about other things, reactive things, um old hematoma. So, here I even wondered at first on the first slide, I thought, could this be an old hematoma? Um, and I saw the hemisin hematidin, but then I saw that big sheetlike cellular area in the middle and I thought for I've seen a lot of organized thrombi and blood and fibbrin but I've never seen that much cellularity and there are some scattered pleomorphic cells in the midst of that.

[00:48:02]So I thought there's no way this can be an organized thrombus here. So I have I've seen a fair number of angomid FH in my career. I've never seen one with this much hemoceterine and this is also the oldest patient I have ever seen it in.

[00:48:15]This is usually a tumor of childhood and occasionally I've seen it in young adults people in their 20s or maybe 30s.

[00:48:21]67 is definitely the oldest I've ever seen. So in the olden days this was called angiomatid malignant fibrocystic.

[00:48:28]It was thought to be a saroma. But then over time people realized that these did not behave aggressively like sarcomas do. They do have the ability in a subset of cases to metastasize to regional lymph nodes. So they can recur locally.

[00:48:40]They can sometimes give regional lymph node METs. And a more aggressive disease like distant METSS or death from disease is extremely rare. I think maybe there's been, if I recall last time I checked, one report of a distant MET that was fatal ever in this tumor. So in general, when I sign these out, I say that these are a tumor of intermediate malignant potential. Basically, you know, uh occasionally metastasizing, but you know, but rarely distantly. And I make a comment that more aggressive behavior is extremely rare. So they should be excised with negative margins. This case it was was narrowly negative and I thought it was probably reasonable to follow up this patient if I recall. Um and uh the uh the other thing that's unusual about this tumor is it it has a transllocation but it has three different transllocations it can have.

[00:49:24]The most common one is EWSR1 fusion with KB uh KB1 KB. Yeah. Um and then the second then the other two fusions are um EWSR1 ATF-1 or fuss fus ATF-1. And the weird and interesting thing that when I first learned about this in fellowship that blew my mind was EWSR1 ATF-1. What is that also positive in? A totally different tumor that looks and stains and behaves 100% differently from this tumor here. Does anyone know what else has EWSR1 ATF-1?

[00:50:01]>> Okay.

[00:50:02]>> And type it in the chat if you know it.

[00:50:05]It's um clear cell saroma. Yeah. Which was in the past known as melanoma of soft parts which stains and looks a lot like a melanoma and is kind of aggressive. Is quite aggressive actually. So that blew my mind in fellowship. Now that we know a lot more about molecular, it doesn't blow my mind as much anymore because we know lots of things have the same fusion in totally different tumors, right? We're seeing molecular answers some questions and then creates a whole bunch of new ones.

[00:50:29]So, um, this is also a good exception. I love what our tour just said a minute ago about when you see monotonous nuclei, uniform nuclei, always think of a transllocation tumor. Mark Edgar taught me that in fellowship and I thought that was such a brilliant pearl.

[00:50:43]Most transllocation associated tumors are monotonous and uniform but angiomeid FH is a potential exception. There are some exceptions and this is a most notable one. These a fair number of them have scattered pleomorphism. Um and they can have a lot of rules that they break and uh my friend Summer Bowman who was a co-fellow with me at Emory when I was a she was a search path fellow when I was a soft tissue fellow. She went on to do her soft tissue training at at Cleveland Clinic and she and Steve uh Billings wrote a really nice paper about unusual exceptions to the rule in angiomatid FH.

[00:51:15]It's a really excellent paper. I encourage you to read it. Has lots of examples of of times where angatoid FH doesn't follow the rules and doesn't look like it should. So this is easy to get mistaken because of the variability of its pattern. The other thing I always mention when I sign these out in a comment because I've seen people get confused clinically about this. They think oh fibrocystic so it's just like a dermatop fibram right so no it's not the same thing it's not at all related to benign fibrocystic which is the same thing as dermatop fibram so I make a comment that despite the name this is totally unrelated to benign fibrocystic/ dermatopyram is totally unrelated so anyway >> okay let's move on to case number three >> those are the most esoteric ones the other ones are a little bit more straightforward >> yeah and just talking about you mentioned Steve billing. So we did a dermededia course uh two years ago and it's available on demand and we you know we amazing amazing derm path and soft tissue pologist really great.

[00:52:15]>> Yeah we it was this was actually the best uh course ever on dermedia really it's such a great update uh for everybody.

[00:52:28]So the case number four, young adult men with soft nodule on on the trunk.

[00:52:38]And here is the H& busy.

[00:52:56]Yeah, quite >> you know in a routine practice when I get a case like that it's I don't like it [laughter] >> because you just say oh gosh it's going to take >> slow down the day isn't it >> it's going to take time or >> you know but as a console I enjoy them you know because that's different kind of a setting but I hate if case like you know busy soft tissue case breaks my otherwise uh you know Smooth sign out.

[00:53:29]>> I know. The older I get, the more I just want to see sea kerattosis and basil >> cells. I like BCC's >> finish it and go home. Yeah.

[00:53:36]>> Yes. Yes. Yes. So, so yeah, it's it's kind of a you know, and you you did not provide any immunos for this. So, we're just trying to >> So, just trying to kind of get an idea of what the diagnosis might be on the H& is there any particular area that you want me to >> if you go uh to Oh, hold on. I can pull it up on my end. If you go to low power, I think it's maybe right down towards the bottom of that. Okay. First of all, see that little stripey area right under where your arrow is, right? This is such a cool. It's like there's like tiger stripe kind of pattern. That's what I call it. I don't think that's a specific thing. I just thought it was so cool in this case that it's got these like rows of round cells. Kind of like a round looks like a round blue cell tumor almost, right? But the cells are very small and very bland and and not like hyperscellular sheets or mitoically active, but they look so round, right?

[00:54:33]Um >> little rosettes or some kind of a glass.

[00:54:35]>> Yeah, almost like little rosettes.

[00:54:36]There's some areas that are a little more spindly. Let me pull this up on my end to find there is an area that has the the diagnostic >> here. There's more of that tiger.

[00:54:46]>> Yeah. And then very, you know, really extensive fat trapping, right?

[00:54:50]Honeycomb. Uh really, if you if you will.

[00:54:53]>> Um so I see someone said, "What about, you know, DFSP?" So the thing about DFSP is usually it doesn't have round cells, right? It's usually thin elongated spindle cells, not round blue looking cells like this. And mixoid lipos saroma. That's a really excellent idea, too. They can have little rounded cells, not usually so cellular. They do in the more high-grade form or what used to be called round cell liposaroma.

[00:55:16]>> So, gosh, you know, on the mentter, you can >> Oh, yeah. Sorry, I forgot the up the chat. Sorry.

[00:55:22]>> No, that's that's that's that's okay.

[00:55:25]>> Got ahead of myself here. you know, we have So, yeah, I'm just going through around, but you know, I really welcome we welcome your suggestions >> and I I'm going to load maybe 20 seconds.

[00:55:47]When you pull it back up, I'll show you where the the clue the key to the D >> because I I thought I knew where it was and I just had to refresh my memory.

[00:55:57]Been a little while since I >> Okay, I'm back on that.

[00:55:59]>> So, on the top piece near the bottom near that green ink, just right dead center of the screen, go in closer.

[00:56:06]Uh-huh. And then right along that ink there, uh, scroll a little bit to your Let's see. I'm trying to match the the piece there. Where are you? You're at Oh, yeah. Go a little to your left. Uh, past that crevice. Keep going along until there's like a big pink bundle over to the Keep going left. There's a big pink area right there and a couple little blood vessels above it. Oh, right there. There you go. That's the key.

[00:56:34]>> Okay.

[00:56:34]>> So, now the diagnosis.

[00:56:38]>> So, let's see.

[00:56:39]>> Is a great idea. Great idea.

[00:56:40]>> So, people thought you guys didn't do that. Great.

[00:56:46]It's a hard case.

[00:56:47]>> It's a hard case. Yeah. So, so, so, yeah, it's a hard case. So, so yeah. So, what's what's your kind of dissected for us?

[00:56:57]>> So, yeah, this is a this is a case and I I had thankfully seen one. This is not the example that I saw in fellowship, but I saw one kind of like this in fellowship, and Dr. Weiss instantly recognized it and said, "Oh, yes, this is diffused nerve fibram." And I was like, "But but it has round cells." And I'm so glad I saw that case because it's so different than the neurop fibramas that we otherwise see, right? This doesn't look at all like a the cutaneous nodular neurop fibramas or like the plexopform neuropyramas. So then Dr. Weiss said, "Oh, it's because diffuse neurop fibramomas the cell the schwan cells are often more rounded and and not as elongated as other forms of neuropyram." And so sometimes they can have zones that look kind of like slightly cellular round blue cells.

[00:57:39]still very bland and just like all neurop fibramas very rare mitosis.

[00:57:43]Mitosis are very infrequent in neurop fibram and then when you look around the fat trapping is not surprising at all.

[00:57:49]Diffused neurop fibramas usually ent trapped fat and when you have a spindly diffused neurop fibram some diffused nerve fibramas are totally spindled and don't have any round cells like this.

[00:57:58]The round cell ones just are really weird and they confused people. I think they confused me when I first saw it. So the spindled ones though are another trap because because they trap fat, they look a lot like DFSP. And guess what?

[00:58:09]Neurop fibramas are positive for CD34.

[00:58:12]So if you think DFSP and you do a CD34, you're going to get burned. So always remember in your differential if you're thinking of DFSP, if there's any chance it could be diffused nerve fibram, add an S100 or a SOCK 10 to make sure. And that will easily sort this out because that's going to always be positive in a neurop fibram. whereas CD34 will be positive both in DFSP and in diffuse neurop fibramomas. So the structure that uh we were showing you down at the bottom there near the ink that's called a uh Wagner Mner body uh and those are basically uh the tumor recapitulating mner corpusles that you see the fine touch receptors tacttoid receptors in the the palmar and plantar aspect of of your finger pads and toe pads and they look like a little clustered aggregate of mner corp pusles there and they are most commonly seen in diffuse nerve fibramas you don't always have them but it's really nice when you have them, boom, you got your answer. The other place you can see these much more often is in neurotized nevi, right? Nurotized nevi make a very similar structure that looks to me just like this. And some people call those misan bodies or tacttoid bodies, but I I basically think of them as just the the neas version of Wagner Meer body. Okay, so that's a really nice clue. And of course, if you did S100 here, it' be positive. This patient had um NF1. Okay. And so uh diffuse nerve fibram is the is the second most common type of nerve fibram in NF1 patients. You know plexopform is the kind of synione uh you basically that diagnosis of plexopform NF. You are giving someone NF1. So don't ever make that diagnosis lightly. And then uh diffuse nerve fibramas are very common in NF1 patients and sometimes coexist with plexopform. I've seen like plexopform nerve fibram with diffuse filling the space in between. But you can also get diffused nerve fibramas in uh regular sporadically in regular patients without NF1. If you see a diffuse nerve fibramis that's really big and weird though that's the kind of time where I get a little more concerned and make sure that clinically they've done a good physical exam to make sure the patient doesn't have subtle NF1 because not every NF1 patient is covered in neurop fibramas. There's a variable penetrance and sometimes people have deep plexopform NFS and their skin looks basically normal or they may have just a couple little neurop fibramomas or a few cafe macules. So I've met patients like that where I was shocked. They're like, "Oh yeah, I have I have NF1." And I said, "What?" And they said, "Yeah, look, I've got a couple nerve fibramomas." And then they had a big deep plexopform one that had been diagnosed on imaging. So that was really mind-blowing when I met a patient like that once a long time ago and really opened my eyes that that not all NF1 patients are like the books show.

[01:00:43]Spittle is a great uh possibility too.

[01:00:46]They can really look neural. And I always say if you think you have a neural tumor, but then it's S100 or SOCOX 10 negative. The short list of differentials I think of spindle cellipoma, perinuroma, DFSP and low-grade fibromyoid saroma because all of those have kind of a neural look but our S100 negative.

[01:01:04]>> Great. Brilliant. Very nice case. I really enjoyed it. That's that's very pretty. And >> yeah, it's beautiful, right?

[01:01:11]>> Yeah. Old-fashioned derm [clears throat] path morphology.

[01:01:14]>> Fashion. That's right.

[01:01:16]>> Case number five.

[01:01:18]Um I'm really looking forward this one.

[01:01:20]uh adult men with rapidly growing ademus painful nodule on dorsal hand.

[01:01:32]So here you have to lead me a little bit.

[01:01:35]>> All right. Well, we can do the low power, you know, we can piece together what >> what we're seeing. And I think that that there are some low power clues here that help us get to the diagnos.

[01:01:45]>> A lot of epidermal pseudepilas epidermal hyperplasia. Looks like >> Yeah. Dramatic, right?

[01:01:51]>> Dramatic.

[01:01:54]And then there's some kind of vascular component, an inflammatory component >> and tons of edema, right? The paperis is just >> so loose with edema in the background wherever there's not vessels.

[01:02:14]So, I'm really curious to see if anyone can get this from what you're showing them here because I think it'd be fair to have several things in the differential. Um, and I would have several things in the differential, you know, seeing a case like this. This case I don't get the credit for diagnosing.

[01:02:29]It had been diagnosed uh prior to me.

[01:02:31]It's from a long long time ago, but someone gave me the recut of it and then I found out the history. So, uh it's just a lovely example though of something that I don't see very often.

[01:02:40]Oh, there. Perfect. You found the the area. Good job, Arur.

[01:02:45]It's not your first rodeo.

[01:02:48]>> Well, it's more a matter of luck.

[01:02:51]>> Yeah.

[01:02:52]>> Yeah. So, so here I think what you are referring to is that the squamus lesions, you know, how do they look that they cytology? Is there anything abnormal there? There kind of a smudgy nuclei. I guess that's that's the key here perhaps. Right.

[01:03:09]>> And then there's some little Well, I don't want to give it away. I want to see if anyone knows uh what what it is here. Uh so you probably can run your menty uh voting.

[01:03:19]>> Yeah, let's do it. Let's do it. Yeah. So what is your diagnosis on the menty?

[01:03:27]I'll keep showing this around.

[01:03:48]Okay. So, let's see. Give 10 more seconds.

[01:03:52]Oo.

[01:03:56]Wow.

[01:03:59]Okay.

[01:04:02]Orphan capacy. That's a cool idea. I like that.

[01:04:05]orphan capital. Yeah, I mean why why not you know those >> why not right >> during HIV epidemics that would be >> very likely baselitosis and um yeah so you see here you can really appreciate the quality exceptional quality of the Dedia audience >> yeah good job guys wow >> your diagnosis or I I thought it was a fascin I you know when I saw this case said gosh you know um it's kind of amazing to to to make this diagnosis So the nice thing about ORF is when if you think of it then usually you can get some history that will end up really helping a lot, right? Because ORF is a a pox virus that's contracted from goats and sheep, right? And it's actually relatively common in animals. Um and it goes by the name scabby mouth. Um so most people that raise goats and sheep are like farmers are pretty familiar with this. And even though I rarely see this biopsied in my practice, I've only seen a few cases in my career. Um, there have been studies that looked at areas where there are lots of uh goat and sheep farming. I think maybe one of the studies from Australia or New Zealand where when they surveyed farmers like about 25% of them had reported that they had had lesions that that were consistent with ORF, they just they recognized what it is and they didn't go to the doctor. They know it'll get better in a couple weeks and it'll be fine. So um the uh the ORF is a little challenging because it is a a process that's a virus that that has different stages right so as it progresses it gets more and more ademinus then you get this massive expansion of the papillary dermis the rei get really elongated and very very thin so that is the one thing here it looks like stupithelomas hyperplasia but you can see some areas the rei are like extremely narrow which is a little weird because usually when we see reactive pseudepitheloma hyperplasia it's kind expanded, dilated, and there's some of that here, but there's also these really thin, delicate kind of stretched down rei. And then as the process progresses, it begins to develop this brisk, robust, reactive vascular component under it. And then when it gets like that it can mimic a vascular lesion like capaci or vasangomitosis or pio pyogenic granuloma you know lobular capillary mangioma even though admittedly it's not as lobular and usually you don't see so much edema in a PG but I think it'd be very reasonable to think of any of those those things and then the classic thing you're supposed to find is in the epidermis in the keratinocytes you should see these little red or pink eosinophilic inclusions that are supposedly viral inclusions. So there are some, you know, pink blobs there, but I don't know like if you go up just a little bit, uh, Arturous, from where you are, uh, like towards the top of your screen, if you just scroll like just a few keratinocytes higher or not that much, >> same area you were at just a couple keratinocytes up, there are some little globules. The problem is I see lots of little eosinip globules in tissue, especially when there's blood, when there's serum. So, right at the bottom left corner of your slide, there's a a little dot, a little pink dot in a keratinocy in the actual like spinus layer down below the serum. If you zoom in a little bit, like right in there, there's a couple dots. So, there you go.

[01:07:17]That little pink dot just below your arrow. Is that an orif inclusion? I don't know. I'm not 100% convinced because there's some little tiny tiny dots next to it. So, I have to tell you, that's the test answer, guys. But in real life, I find these challenging to recognize. I mean, I can always find a little pink blob if I want, but am I really convinced that's a viral inclusion? No, I'm not. So, maybe better people than me can do it. But what I I like better is if I think about ORF and then I find out, oh, the patient recently had goat or or sheep exposure and we know that this makes sense, then great. Um, I saw a case a while back that we're pretty sure was orf, but it had tons of neutrfils in it and looked almost like sweets clinically and microscopically, but had tons of edema and long thin rei uh, but it was on the scalp of a of a little kid. And it turned out the little kid had been to a goat farm uh, a goat petting area just a couple weeks previously and his head height was about the height of a goat's mouth. And so goats love to chew on everything including hair. So our we we postulated that. We're still working on getting it published. uh the journals are like well we really want EM so we're going to try to pull the case and see if we can run EM to prove that there's virus there we found in that process we searched a lot of labs and no labs do molecular that we could find for ORF in the United States on uh patient samples there some uh animal labs will do it but so we really thought oh this should be easy but we couldn't find anyone so if anyone out there knows how I can get uh a viral or IHC testing we even checked with the CDC they have a stain but they said they cannot do it on a clea patient a human patient sample unless it's a pure research sample. So to our sadness, we couldn't get it there. So if anyone else out there knows, I'd love to to hear from you so we can prove our cases or our other cases or with neutrfils.

[01:08:59]But pretty cool. Uh pretty cool and something we don't see often. Um I see Dr. Tyler's on here. He was a a colleague here with me in in Danville.

[01:09:07]Uh and then he retired around the just a bit after I started. And he said that sometimes we would see cases in Pennsylvania after the the Bloomsburg Fair, which is the town I live in. And it's a huge huge fair that's going to happen in uh I think tomorrow is the first day it opens because they have uh animals there, lots and lots of animals.

[01:09:22]So sometimes occasional cases will pop up after the fair uh because of increased exposure to goats and sheep.

[01:09:28]So there you go.

[01:09:30]>> Yeah. Wonderful. patient actually also I remember he was a transplant patient and he had cut himself while slaughtering a a goat with a halal goat slaughtering for a a festival and he accidentally cut himself with a knife that had the goat blood on it and then um then he developed or later and his case was pretty severe because he was immune suppressed they ended up I think they gave him like antiviral therapy and it finally went away but he had a much more robust case than usual because he was immune suppressed or that's what we theorized it was a long ago I don't remember all the details Yeah, great really great case. You know, I was just trying to find uh a case on Dermedia and we we because I had a consult that I shared. So, you can go and find it if you search for ORF. Uh there are cases um there too. Yeah. Wonderful. I think that that really expanded my differential diagnosis because I wasn't really that it wasn't I wasn't that familiar with that pseudo epithelus hyperlasia. No. So extreme and the vascular part too when I saw this case first I I didn't conceptually know that >> that's the late that must be the late stage you know the virus is gone >> there's this kind of residual >> uh process >> so case case number six and you have 80 year old man with a papule on the nose and a case that taught you very important lessons >> very important lesson >> yes very important lesson I wonder what that might be uh and and let's take a look at the H& so we're going to do the H& and we're going to to share with you the imunostochemistry very busy Pleomorphic spindle cell neoplasm. Yes.

[01:11:33]>> Yep.

[01:11:35]Ugly cells fill in the dermis and old sun damaged face skin.

[01:11:39]>> Right.

[01:11:41]>> Sorry for the folds. There's that case from a long time ago. I didn't have a way to make new slides, but it'll have to be good enough.

[01:11:49]>> That that really testifies to the authenticity.

[01:11:52]>> That's right. He definitely want to you know improve on nature really. Yeah. So that that's that's the I think hisystologology and let me share with you the imostochemistry. The tumor cells were negative for SOCK 10 S100 panyotin P50 P63 Desmine and CD34.

[01:12:22]And the question for you now is what is your diagnosis?

[01:12:29]And we'll ask that question. I think again there are some clues to that diagnosis maybe on the H& >> but >> there are they are subtle though.

[01:12:42]>> Very subtle.

[01:12:47]>> So I give you uh 20 seconds on the manter.

[01:12:54][laughter] >> True fans know this case. Someone has been following cuz I have posted this case quite a few times before actually.

[01:13:01]No, I should have thought of that. I should have known.

[01:13:02]>> Come on. This is the this is Derpedia.

[01:13:04]This this is the most advanced group of dermatop pathologists on this on this planet.

[01:13:09]>> It's awesome.

[01:13:10]>> You know, these are not students, you know. I I didn't expect anything else, you know, and saroma is the diagnosis.

[01:13:17]>> I think this is a caseedia audience.

[01:13:21]>> I'm so proud.

[01:13:22]>> What you do would you do next? And you know, you shared the imos CD34.

[01:13:28]>> Just in case you didn't believe me, CD34 is negative. It is negative. Like totally negative. You can see background vessels that are positive. There's your DFSP control up there. And here the background vessels positive. The tumor cells are completely negative for CD34.

[01:13:42]>> Okay.

[01:13:44]>> But urg you don't even need a microscope, right? Blazing positive.

[01:13:50]>> CD34.

[01:13:52]CD3. Sorry. 31.

[01:13:54]>> Yeah. And you can see I love to write on my slides with markers and it I sometimes I forget to mark wipe it off.

[01:14:00]So um you can always tell in in my department if a case is mine if it's got blue marker or purple marker all the slide it's my case.

[01:14:08]>> So spin cell and saroma >> mimicking um AFX but you know how many how popular was the diagnos of AFX? Uh let's just >> who's on there but smaller >> on there. Yeah. Yeah.

[01:14:25]Because I I think you know that leion actually the H& you know those holes those little >> Yes. Good >> vacules. Right. So I think there's a few clues the little the little vacules endothelial tumors particularly angiosarchic epithelial hemango endotheloma they make they tend to make little vacules sometimes kind of like in in ehe they're called blister cells right but we can see similar kind of vacules in angio saroma and sometimes in other things like epithelial hemangi alhe make little vacules not they don't look like this but they make vacules so the other thing is you can see this kind of like nested area at the top that's probably a vascular panel that has completely been filled with tumor cells.

[01:15:05]That area with the crack over at the right there just below the epidermis.

[01:15:09]It's kind of this long kind of a serpigenous structure that was probably a vascular channel formed by tumor that then filled up. So my my partner uh Jackie Jun Hopkins um here at Gisinger, she likes to say it's that um the angio saroma the endothelial cells are like fish in a creek. They're like swimming and filling up the middle of the creek.

[01:15:28]And I think that's true. And sometimes they get so full that they completely overrun the center of the creek, the lumen of the spaces and they become solid. If you have a big enough sample, these solid angio circumcis usually will have areas of obvious vaso formation.

[01:15:42]But on a small shave, you sometimes don't get any of it. So you have to have a high index of suspicion. So the other thing is the blue gray kind of this slate gray blue color ampilic cytoplasm.

[01:15:54]Andrew sarcomomas, especially the more epithelioid ones, the more cellular solid ones, they tend to get this bluish gray look to them and um in a way that you don't see as often in in say you know AFX or other other entities. So that kind of bluish gray or amphopilic quality and also the cells are kind of plump and epithelioid. Can you have epithelioid atypical fibers or pleomorphic dermal saroma? Sure you can.

[01:16:18]Is it common? No, not in my experience.

[01:16:21]Anytime I see something that I think is an AFX or PDS spectrum, uh, but is pretty epithelioid, I'm always extra cautious to make sure I've excluded all the other stuff because I've seen a variety of times where things that were looked like AFX but were more epithelioid ended up being angio saroma, epithelia saroma, and other stuff. And these are things that are much more aggressive. Angio is a very aggressive malignancy uh much more concerning than AFX or PDS. So if you look back on the CD31 Arthur, I think you can actually see some vaso formation. One of the stains shows it. I think it's a CD31. It just wasn't really obvious at all on the H&. But on one of the imuno stains, that deeper cut showed a little area where there's an obvious vascular channel. Let me see if I can find the area on the slide here. I think it's 31 that had it.

[01:17:11]So the lesson I learned from this case is angio saromomas can be CD30. Yeah, look at the right there on the right side. You can see that that what looked solid as you go over to the right edge of the shave opens up and it's a vascular lumen now lined by multi-layered atypical endothelus right there. So, so again, maybe even just deeper H& cuts would have made this obvious, but this was the the story behind the case is a long time ago. A colleague, a friend of mine sent this case to me and said, "I think it's probably AFX, but something's kind of weird about it." And he had already done the CD34 and that whole panel of stains and still was like, "I still feel like it's a little weird. there's a little vasa formation at the very very edge there probably or discohesion at least you know um the uh so I saw and I felt the same thing I was like maybe it's an AFX but it's kind of weird and I I thought a bit about angio saroma and even though 34 was negative I added URG and CD31 both of which were blazing positive and so the part of the reason I was able to get this was a story shared by and said that he had mistaken uh angio saroma once and thought it was an AFX and it was one of biggest mistakes he had made. And I thought that was such a brave thing to like openly share that with the audience. And thank God he did because I thought better soft tissue pathologist and dermipath than I'll ever be. And if he could make that mistake, then I sure as heck could make that mistake. And it was this case came in about like six or eight months later.

[01:18:34]And it was because of that memory and that fear of thinking, "Oh my gosh, that's scary." Um so because of him saying he always you know wants to keep that in the differential and not mistake an angioarch that was solid as an AFX.

[01:18:46]So I started adding a vascular marker on my routine panel which I had not done originally at the very early stage of my career and it was uh and because I knew that CD34 sometimes is negative in angioarkc and this one worried me enough I added the urg and the 31 and it proved the diagnosis. So now my routine AFX PDS panel I pretty much always include either CD31 or URG. URG is my go-to.

[01:19:09]Just so you know though URG is very sensitive but it's not specific. It can stain uh AML uh acute myoid leukemia.

[01:19:15]Stains prostate cancer which of course is extremely rare in the skin. Stains about 50% epithelioid sarcomomas and other stuff. But it is very sensitive and super strong in angioark. And it should look like the case we just showed you here. anything patchy or weak or like staining some of the cells and not other not angio saroma okay if you an AFX often has some patchy URG staining you can just ignore that don't worry about it it should look like four plus positive 100% of the cells as strong as the background vessels that's the way URG stains vascular tumors it's if you have to ask yourself is there enough URG here the answer is no probably not it's probably not vascular if you're if you're questioning that usually you just look at the slide with your naked eye and you're like whoa is positive. So anyway, this is a great case about like the benefit of sharing mistakes we've made and challenges we've struggled with because our trainees can learn from that. It's a great example of having awareness that angioart can be solid and can be spindly sometimes and can mimic other sarcomomas when that happens and usually it's on a small shave like this is when the big problem happens. Usually again you'll find vessels if you look around enough or get a deeper bigger sample but you don't always get that up front. Sometimes angiosarchs don't have any violations colored clinically.

[01:20:30]Sometimes they don't have any blood filled spaces microscopically. I've seen multiple cases. I've also seen capacity that way where there's no blood at all.

[01:20:37]And when you don't have any blood filled spaces, it's real easy to not think of a vascular tumor. So these are this whole theme of the session has been vascular tumors that look like they're not and non-vascular tumors that look like they're vascular, right? And I think that's a good thing is that we can get confused either way. So, so I I again I big plug for either URG or CD31 and and I would recommend against using CD34 as a screening marker for vascular tumors.

[01:21:02]It's often positive in angioaroma. I would say even usually, but I've seen many examples now of angiosarch that were partially or completely CD34 negative. So do not trust CD34 alone for ruling out angiocaroma. Okay. My AFX PDS panel personally and everyone's got a little different view. I like to do a high molecular weight keratin. Uh, in my lab I think CK56 works best. Uh, some people uh like CK93. Some people like PAN keratin. That's fine. I feel like in my lab CK56 works better than PAN. I also like to use a nuclear marker like P63 or P40. P40 is what I currently use because it's cleaner. If you don't have that, you only have P63. That's fine. I know some very good dermatopathologists that don't like P40 or P63 because it's kind of a little wishy-washy and that's okay if you don't want to use that. And then I usually use a sock 10 as my melanocytic marker to rule out I know some people who like to use more than one melanocy marker. That's okay if that's what you want to do. And then I usually use a desmondine to rule out um rabdomi saroma which is really rare in the skin but it does happen and it's very bad and aggressive when it does.

[01:22:03]And then also limyio saroma which is part of the so-called slam differential.

[01:22:07]But I'll tell you honestly, I don't think I've ever seen a case of actual liomi saroma in the dermis. That at all confused me for AFX or or spindled squam or spindled melanoma. They lie sarcomas in the skin look like lom saroma and they're usually on the trunk or maybe the extremities not on the face of old people at least. I don't know. Arthur, have you seen very many liaromas on the face of older people? I think I've seen one >> really but but I've seen uh Eric positive um >> Eric positive in some areas um not diffusive positive um AFX so and I shared and I I shared a few examples actually under PDMI console session so you can just URG if if you search uh you know you'll find I think one or two >> yeah it's almost like a a feature like it's more like a lot of tumors are cleanly negative for URG but AFX often has patchy staining as long as you know that patchy is okay don't worry about it >> and D240 can be often positive also in squam so one has to be always but you know I have to tell you in this case you know my differential diagnosis would also include a hemango endotheloma >> because there's certain kind of uniformity of again the cellularity you know and u I would wonder um you know if if that lesion could also I mean that's certainly in a differential diagnosis that one of those fusion driven >> like an epithelio imagin rearranged >> oh yeah >> yeah just just a fusion you know because there's certain monotony like I usually think of angio sarcomomas as very being very pleomorphic more more pleomorphic than this case and so so you know just just something to consider um in to expand the differential um diagnosis uh in in in a vascular tumor that >> yeah you know >> and so if you're thinking about that for the audience you know that would be a good time to do like an NGS fusion panel to to make sure that you look for the WWTR1 CAM to one Yakap1 TF3 and others um and so I think that's a that's a good thing to to think of and and there is a big difference because angiocomomas are quite aggressive they get really uh aggressive treatment and have a a very guarded prognosis um I've met people that are long I I volunteer in an angio saroma patient support group on Facebook. I've been doing that for over a decade now. So I've met some long-term survivors from angio saroma which is amazing. But I've also met a lot of people who who died and and family members of people who died quickly from angio saroma. It's a horrible horrible tumor and very serious and and and much more serious and aggressive than most of the other things in the differential. So really important to always keep it in mind. and hemangonethelomas depending on which type are are you know sometimes they can metastasize the epithel one uh but the other ones are more like locally aggressive not as often metastasizing so they are not as uh as um as aggressive of a a disease as angio saroma so important to make that distinction great point I think we exhausted our time uh you know we exceeded this hour but as you know we're not really on on any time schedule uh doing the work.

[01:25:25]>> Everyone who watches any of my videos knows that I I always go overtime on everything, so they're probably used to this.

[01:25:30]>> Yeah.

[01:25:32]>> Okay. So, you know, thank you very much.

[01:25:33]Let's see if there are any, you know, final questions on chat. If someone asked about can pre become positive in pleorphod dermal saroma. I don't know. I I don't usually use preme unless I'm trying to figure out if something's melanoma versus neas. So, I've not really applied it. I know that like differentiated melanomas which are rare but do happen they usually are diffusely prime positive and and so that is a question that comes up but I've not used I've not tried preme on enough cases of like afx pds to know like how reliably negative I think there was a paper last year by Jason Hornick and colleagues from from Brighamin Women's about using prem on diff melanomas and they did I think look at some AFX and pleomorphic dermal saroma but I've been a little hesitant to include it in my panel because I just don't have enough experience to know like what will I do if I've got some patchy pre positive or even diffuse positive and everything else melanocyic is dead negative because raising like oh this is AFX PDS but maybe could be diff melanoma I mean like that's a pretty big difference you're bringing up there and so I I've been a little hesitant about that but I think that's a great question and and I don't know do you use preme in your panel of AFX >> no but you know any anytime there's a you know possibility that the leion could be melanoma. I think a lot of effort has to be spent.

[01:26:54]>> Yeah.

[01:26:55]>> To to to confirm that and probably now the best way to go about it is just to do NGS, you know, look for melanoma, >> you know, signatures because of the treatment, you know, if it's melanoma.

[01:27:06]Now, a melanoma is a good news.

[01:27:08]>> Yeah. Paradoxically, right?

[01:27:10]>> You know, it's it's it's a good news because there are good treatment options.

[01:27:14]>> So, Jarrett, thank you so much. Thank you for for doing this uh you know workshop and um >> really showing your >> thank you everyone for showing up. This was really really great.

[01:27:26]>> Incredible ability to describe things.

[01:27:28]You know you use you use at least you know 10 times more words than I can really uh come up with. [laughter] >> I have probably spoken several languages but you spoke very well. You know, it's it's it's it's fun to >> uh to to to watch.

[01:27:43]>> I've been talking a lot since I was a little child and I've never stopped since. So, >> yes. And you and you find you found a niche that allows that and actually uh creates an audience of people who are very grateful for your efforts.

[01:27:56]>> Thank you.

[01:27:57]>> And you know, so am I. And so is the audience of today's workshop.

[01:28:03]>> Awesome. I hope to, you know, see more of you and >> and actually guys, there are those little hearts that you can see just, you know, if you like this idea, h how about putting Gerald on my short list of folks who could take over Duredia when I retire? How about that? H is this a good idea?

[01:28:29]Look at the hearts.

[01:28:30]>> Not hard. Just >> Yes.

[01:28:33]Okay, actually he is on my short list.

[01:28:35]So, >> okay folks, thank you so much. Thank you everybody. Thank you.

[01:28:40]>> Have a great everyone. Bye.