this is Merkel cell carcinoma or a primary cutaneous neuro endocrine carcinoma and these tumors usually arise in sun-exposed areas in older individuals and most importantly they're really important to recognize because they often be quite aggressively and a significant number of patients will develop metastasis and eventually died from disease so a really bad tumor and you definitely want to miss it and from low-power kind of a blue tumor filling the dermis and an older sun damage person really easy to think about basal cell carcinoma in some cases so if you're just looking at low power and not thinking about it it'd be easy to make that mistake and that's a real pitfall because even though they're both carcinomas basal cell carcinoma is very rarely causes mortality and this tumor commonly does and they're treated very differently so it really important to learn to recognize if you see a cellular large blue looking tumor or a carcinoma looking it looks like a you know kind of like a basal but real dark and real cellular from low power always think about merkel and if you even think about it go look closer and and take some time doing that to make sure that you're not missing that so let's go a little closer and look and like I said Merkel's cell carcinoma is actually a form of neuro endocrine carcinoma that arises in the skin and it has similar features to those seen in other types of Narenda cream carcinomas particularly small cell carcinoma of the lung so if you know what small cell carcinoma looks like in the lung you basically know what Merkel's cell looks like it has a lot of similarities histologically so the cells are arranged in kind of nests or aggregates sometimes they can be sheet-like and diffuse sometimes they can make large nests other times small nests one big difference that you couldn't you'll notice when you look a little closer is they lack the basal Palace ating that's seen in basal cell carcinoma so basal cells usually have palisaded nuclei around the outside and it's pretty uncommon to see that in Merkel's cell I've seen it before but it's not very common so even though these are blue and kind of basal oyd they don't arrange themselves in the same way that basal cell carcinoma would and if you look closer at the nuclei the nuclei do like I said they do similar things to what you see in other types of neuro endocrine tumors for one thing they have this very kind of pale or fine smudgy chromatin people use salt-and-pepper chromatin and I I don't really love that term I think it doesn't really look like salt and pepper to me but people say that I like the the words stippled or fine or homogeneous or dusty kind of chromatin but you know like all visual terms and pathology you have to use the visual term that works for your mind and the other thing is that look at what the nuclei do you can see that the nuclei they clump together and they mold to their neighbor they're squished together and fit perfectly with the neighboring cells they're not perfectly around when they when they bump into a neighbor instead of staying around they kind of squished together and take on the shape of their neighbor like look at that guy he's got kind of a little triangular point on one and let's see if we can get a little bit higher power even for the video yeah perfect you can see those cells are just squished and molded perfectly together they have this very fine kind of dusty smooth chromatin they may have some small nuclei but usually Merkel cell does not have large huge nucleoli so that's kind of a clue and here's a here's again that kind of it's a little bit hard to get the to pick up on the video the exact quality of the chromatin but it does have this kind of stiffled or I guess kind of salt-and-pepper is what people talk about little tiny dots of chromatin in there and occasionally you can see structures like this that are kind of almost rosette like where the cells are kind of making a little little flower shapes so sometimes you can see rosette type of figures in Narender carcinomas that those are nice rosette looking things they're I don't I don't find that a real helpful diagnostic feature but it is something you can see and I've seen some that we're even kind of spindled looking so they don't always have this exact this exact pattern but in any case this is a Merkel cell and you probably have noticed already there are mitosis everywhere in this tumor these tumors are some of the most mitotically active cancers of any of the cancers that I see in my practice and the the mitotic rate we when we when we diagnosed Merkel cell we provide some prognostic parameters including the mitotic activity in the depth of the tumour and some things like that and the mitotic rate for you know say for a melanoma the mitosis you may have just two or three mitosis or for a bad melanoma maybe five or ten mitosis in a millimeter squared which on my microscope is about three and a half high-power fields every microscopes a little different on Merkel cell I've had I think my highest that I've seen was a hundred and forty mitosis in three millimeter I'm sorry in one millimeter squared or three and a half high-power field so it amazingly more mitotically active than then melanomas and a lot of times you kind of have a pop taht excels and crush cells so it can make counting my testes kind of hard but let's see right here you can see there's a mitosis there there's one there here so they're they're all over the place in here lots of mitosis so to confirm the diagnosis what I like to do if it looks like this this this looks classic this looks very you know just on H&E I'm basically almost 100% certain that this will end up being a Merkel cell carcinoma but but it's such a bad diagnosis we want to be totally sure so one thing that I like to do is I use an immuno stain cytokeratin 20 and cytokeratin 20 is positive in almost all Merkel cells and it typically not always it doesn't have to do this but it typically has this amazingly beautiful perinuclear dot like pattern or people call this the Golgi pattern sometimes but these dots really darkly staining perfectly punctate round little dots that are in each cell right next to the nucleus look at that amazing so you can see the nuclei here and you can see these dark dots of cited carrots and xx staining which if I have a histology that's classic like this and C K xx positive I feel totally comfortable making a diagnosis of Merkel cell in that setting are there other things that could potentially mimic that I suppose so but very very uncommon now the the main thing that you probably think of and that people talk about a lot is what about metastatic small cell carcinoma from the lung or from other other places well I'll tell you that I see Merkel cell carcinoma pretty commonly in my practice and I've still to this day only seen one or maybe I can think maybe two cases of metastatic small cell carcinoma from the lung in the skin and in at least in one of the cases the patient already had known disseminated disease and the the finding was already known so it wasn't it was it was metastatic but it was because the patient had widespread Mets and the recognizing that it was a metastasis was would not have made any difference in patient care but I think that you know we often worry well what if we call something Merkel and it's actually metastatic small cell so that's very uncommon but the to me the easiest way to solve that is if you do a CK xx CK xx is is a positive almost always in Merkel's cell and very very uncommon to be positive in metastatic small cell carcinoma from the lung so you're you know and you're already in a site where the the odds of this being Merkel cell are much much higher so I feel like that is pretty confirmatory most of the time now if the CK it's one he doesn't work or it's kind of kind of wishy-washy then I can do other stains neuro filament stain works very nicely and often gives you a similar dot like pattern and just of note other types of cytokines like pand cytokeratin will will often stain with this dot like pattern as well so the dot like pattern is not totally specific other tumors can do that and it's not required either you can have diffused cytoplasmic staining that's not dot like in Merkel's cell carcinoma so don't don't think that you have to have dot like sting but this is the typical classic finding that you see so nerve filament will work and then you can use other things like synaptic isin and chroma green and which are neuro endocrine markers and those will stay in here too but I don't usually do those this first line because if it looks so so good for Merkel cell then I just do a CK xx and that solves the problem usually and TTFN one is a marker that's going to be positive almost always in small cell carcinoma of the lung and it's very uncommon I'm sorry it's it's also potentially positive in small cell carcinomas of other site including herckel cell so it TTFN one positivity could potentially be seen even in a Merkel cell if TT up ones negative that would be further argument against metastatic small cell lung cancer if it were positive I would probably put a comment in the report that you know even though that can't be seen in Merkel's cell the patient probably needs a imaging of their lung to make sure that there's not a small cell carcinoma there so but again I don't resort to that as a first line I do that if my CK 20 is negative or if it's not very good then I might add on a TT f1o cited keratin 7 which would stay in metastatic small cell carcinoma from the lung and there are lots of different approaches to this immunohistochemistry is kind of a somewhat of a science mixed with art because everyone has a different approach that they take with cases but is in my approach CK 20 and it's staining a Merkel cell carcinoma