Male Speaker 1: Next presenter is Stephen Ruby, a board certified pathologist. There’s a great deal of experience in this regard. He is lecturer and author. And we thought it would be pertinent at this juncture to have him give us a discussion on the common cutaneous malignancies in the lower extremity. And hopefully, he will also focus somewhat on non-healing chronic wounds.

Stephen Ruby: Thank you. Great. Thank you. Well thank you very much. Like I said, it’s a pleasure to be here. I’m going to ask everybody to take about five seconds just to stretch a little bit. I know we’ve had lunch at two lectures. And if you’re anything like I am, it is a moment to just stretch. Okay. What we can do is get started while you’re stretching a little bit, and my question I have, I have a number of questions for you. And my first question is, there we go, we have to learn how to use this thing. Did you know, well this is going to be tough because you know what, I’m having a hard time reading this. More than three and a half million new cases of skin cancers are diagnosed each year. And that more skin cancer is diagnosed than breast, prostate, lung and colon combined. So this is a common, common problem. There’s more than 700,000 cases of squamous cell carcinoma which are diagnosed annually and 2.8 million cases of basal cell carcinoma. Non-melanoma skin cancer cases have increased 77% from 1992 to 2006 and that 40 to 50% of Americans who lived to age 65 will develop one of these forms of skin cancer. And about 90% of non-melanoma skin cancers are associated with ultraviolet light exposure. And did you also know these things that a person dies from melanoma just about every hour in the United States? And that 1 in 50 individuals, a couple of people in this room will be diagnosed with melanoma during their lifetime. And melanoma is only one of three cancers in men with increasing mortality. And from 1970 to 2009, melanoma has increased eightfold in young women and fourfold in young men. And melanoma, although it comprises only less than 5% of cutaneous skin cancers, is the major cause of death from skin cancers. We have to remember that the five-year survival from melanoma, when it’s caught early is 98%. If it’s left uncaught or undiagnosed, and it goes to the regional lymph nodes, five-year survival drops to 62%. And if it goes even further to distant organs, that the five-year survival drops to a dismal 15%. And the important part about this is you have to remember that failure to diagnose melanoma is a major malpractice risk. I’m Dr. Ruby and we had a brief introduction there. I’m the founder and the medical director of 4Path Laboratories. And today we’re going to talk about the common cutaneous malignancies. And I used three colors here which we’ll see in a little bit. Red represents squamous cell carcinoma, blue represents basal cell carcinoma and black represents malignant melanoma. So in your clinical practices, have you missed squamous cell carcinomas? Have you missed basal cell carcinomas? And god-forbid, have you missed malignant melanomas? In your clinical practices, when you see these lesions, you just guess at the diagnosis and not know what your hand is showing after you’re guessing at these things. Or, if you take a more informed approach and get to know what your hand is, so that you know what you’re being dealt with there from your patients. And the question is, is how do you tell these lesions apart? Okay? Are you just trying to decide whether it’s benign or malignant by your clinical criteria or you’re actually using something that’s a little more comprehensive? Are you using clinical judgment alone or using clinical judgment and biopsies? And the question that you have to ask yourself is why should I bother biopsy? And a lot of people feel that they may not need the feel to do it or need to do that. They just go on their clinical rounds alone. But the fact is, is that, doing a biopsy will unequivocally establish the diagnosis and will allow you to establish your treatment plan and follow up for that specific diagnosis. And also, the important part is, that we always forget about is we’ll help protect you and keep you out of trouble by knowing exactly what you’re dealing with. So today, as we go on further, we have several learning objectives. First of all, we’re going to talk about these three most common cutaneous skin tumors.

[05:01]

We’re going to understand where they arise within the skin. We’ll review some clinical and I have to say this forewarning, some pathology images of these diagnoses. We’ll understand some differences in the biopsy approaches especially from a pathologic viewpoint. What you should expect in your pathology reports when you get your reports back from your laboratory. And most of all, what we’re looking to do is to reduce your risk and keep you out of trouble when dealing with cutaneous lesions. And my disclosure is that I’m the founder and medical director of the laboratory and that’s my full disclosure at this point in time. So let’s go on. Let’s start right into it. Where do tumors originate? And people say skin tumor are very generic fashion. But the fact is, is that the skin tumors, there’s a whole cornucopia of skin tumor. As a matter of fact, I’ve got a whole shelf, just of different kinds of skin tumors arise in different locations. Here is a photo micrograph and it’s a typical piece of skin. We’ve got the stratum corneum here, we’ve got the epidermal layer here, the basal zone around here and then we have the dermis. And again, just a real brief picture. But what I want to show you is that in squamous cell carcinoma originates in this upper differentiated portion of the squamous epithelium. Although the skin generates from the basal zone, as it matures up, it acquires the keratohyalin and it expands out its amount of cytoplasm and it gives out the characteristically pink appearance, hence the red color for using the font in this presentation. With basal cell carcinoma, the lesion or the lesions arising from the cells which are at the basal cell zone. Also squamous cells, the squamous cells which we not have differentiated yet, and you can see that they have a much more blue color, hence it’s the use of blue in the font. Next we have malignant melanoma. And although malignant melanoma arises from melanocytes, which are also at the basal cell zone, that they are a different form of cells. The squamous cells and basal cells are ectodermal-derived whereas melanoma is neuro-crust, so it’s usually dermal-derived lesion. But the cells that are here, they co-mingle with the basal cells, they produce pigment which then is injected into the adjacent cells to produce the pigmentation that we see either in pigment at lesions or at the normal pigmentation of our skin. The next thing that we need to remember, although we’re not going to cover it in depth in this lecture, is that there’s a wide variety of other tumors which can arise within the skin. We can get involvement of the epidermis or the skin by leukemia and lymphoma where there’s infiltrates by either leukemia or lymphoma cells in the skin. We can have skin adnexal tumors and those are tumors that are arising from things like hair follicles, sweat glands, sebaceous glands and so forth. And so those are different. They’re characterized a little bit different than the squamous cells and basal cells but nevertheless they are skin tumors. We can have connective tissue lesions which are arising in this compartment of the skin and that can include things like angiosarcoma, Kaposi sarcoma, both of which are arising from the blood vessels. We can have things like dermatofibromas which are arising from the fibrohistiocytic cells of the dermis. We can have lesions such as smooth muscle tumors, leiomyomas which can be arising either from the smooth muscle of blood vessels or the smooth muscle of the erector pili muscles which cause your hair to stand up when you get cold. And then last, we also have to remember that you can have metastasis arising in the skin. And this is one thing I’ve mentioned at a couple of times already today. And I think this is an important part when you’re looking at pathology laboratories. Although we’d like to think that everything is specialized, when you look at the skin, you look at lung, you look at prostate, you look at the thyroid, I really think that it’s good to have a good laboratory that sees a little bit of everything. The reason is, is because of this reason alone. As a matter of fact last week, we had a case of skin which had metastatic prostate carcinoma. In my laboratory, we see a variety of tumors from all over the body. So when the prostate carcinoma pops up in the skin, we don’t confuse it and try to pigeonhole that into one of these categories saying it’s fold skin, it’s actually metastasis from else from the body. And we’re so used to seeing those that it becomes easier for us to make the correct diagnosis. So the next question that we have to ask is when you’re biopsy-ing, do we want to do an incisional biopsy or an excisional biopsy? And from a pathologist standpoint, it does make a difference for us in a variety of ways. But let’s first of all, let’s look at the differences between the two, the incisional and excisional biopsies. An incisional biopsy, a one that’s just taking a piece of it, will give you the diagnosis. And that’s important and that’s very, very useful.

[0:10:03]

But an excisional biopsy, if the lesion is small enough and you can take the lesion in its entirety, we’ll do two things. Provide you with the diagnosis and also potentially is curative or therapeutic for the patient. Incisional biopsies can be used to determine the definitive approach for example, if you have a much larger lesion, and you try to decide, is this a squamous cell carcinoma, is this, you know, what are we dealing with? That can establish a diagnosis and at that point, you can then go back to do the much more definitive excisional therapy, okay? Whereas the excisional biopsy can be used as a definitive therapy. And I think a lot of times, what’s happening between these two is one, it depends on the size of the lesion and the surgical approach. If you can do it as a more simple surgical approach and an easy closure, then go ahead and do the excisional biopsy right off the bat. But an important thing to remember is in incisional biopsies, there are certain times that if you can avoid it, you shouldn’t use incisional biopsies and you should use excisional biopsies. And I’d like to stress that especially in malignant melanoma or pigmented lesions what you’re suspecting that could be a malignant melanoma. If at all possible, always do an excisional biopsy. The reason for that is, the staging and the grading of that melanoma is extremely critical for determining the right level of therapy and the prognosis of the patient. And we’re talking about the differences in fractions of millimeters. And I’ve seen cases where someone has saucerized or taken the surface off a malignant melanoma or is put in a punch biopsy through a malignant melanoma. And what happens is, we don’t have the whole lesion to be able to properly stage it for the depth of invasion or the thickness of a lesion. And then it’s taken off in the secondary procedure, and they come back with the knowledge and say okay, well you got the two biopsies. Try to put them together and stage it for me, but we’ve got granulations tissue. We’ve got scar and we’ve got everything else, it’s doing the patient a grave disservice to be able to do that kind of process when it can be taken off as a single-stage process. Now, that’s not to say if you have a very large lesion that you can’t do without skin grafting and everything else. Then you want to be able to use it. But judiciously, if you can get the lesion off in its entirety, that’s always the best way to approach. So let’s quickly, look at some different kind of cancers that we have here. Here is a cornucopia of squamous cell carcinoma, some clinical pictures. Large lesion, irregular edge, relatively sharp but it feathers off. And that’s one thing that’s interesting on squamous cells, they can feather off at the edge, obviously, big areas of ulceration. Here’s a squamous cell carcinoma on the lip. And you got a large real border and this is a picture that actually could be confused with basal cell carcinomas. It could cause ulceration there. Here’s a chronic radiodermatitis in the toes, and another one with areas of ulceration on this chronic radiodermatitis here. Probably, most of these is squamous cell carcinoma in situ, but I believe here, you get your ulceration and I’m sure that there’s areas of invasive squamous cell carcinoma in there. And then we can’t forget about our good old friends of Verrucca, longstanding untreated Verrucca, not frequently, but can on occasion degrade into an invasive squamous cell carcinoma, because of long-term irritation effect on that. Microscopically, we could see that the squamous cell carcinoma goes back with my pictures or my fonts said before. It has a kind of a pink hue. We’ve got all these different little nests. We’ve got the little basaloid cells around the edge which is not basal cell carcinoma but basaloid cells and the differentiation. With a little high powering you could see that better. This nice pink coloring of the tumor, where you have the keratohyalin accumulating in the cytoplasm. You’ve got high powered this and that. You can also appreciate some of the nuclear atypia that’s here, nuclear enlargement irregularity, hyperchromasia and a lot of different hallmarks and buzzwords that we use in pathology to talk about malignancy. This is just another slide showing the same type of features but we also have up here some areas of keratinization. And in squamous cell carcinomas, in addition to accumulating that keratohyalin, and getting the more orange parents, they can actually create a keratin layering create keratin pearls. And then a high power again just showing that very formative pleomorphism or that variation in the nuclear size, shape and configuration and coloration. So let’s move on to basal cell carcinoma, and again, we go to the blue color. And there’s a reason for it, and you’ll see that here, why it’s a much more blue lesion. But we got some clinical pictures. And remember back on the squamous cell carcinoma, we had a relatively well-circumscribed lesion with a rolled border and area of ulceration. But this is a prototypical picture for basal cell carcinoma. There’s another type of basal cell carcinoma. It’s called superficial multifocal basal cell carcinoma. Instead of being a nodular configuration, it’s a much more flat one.

[15:01]

It just kind of just goes off and it just trails off. And you really can’t tell where the edge of the lesion is and where it stops and where the normal skin begins. But again, it still had a nice pearly appearance and a little bit of ulceration. And here’s this another picture adjacent to the nose, large, relatively well-circumscribed, elevated edge, ulceration rolled border, pretty typical for a basal cell sometimes. Now microscopically, you can see it looks considerably different than the squamous cell. Instead of having that pink cytoplasm and that red cytoplasm, we have these cords of cells that are much more blue and basophilic in their appearance. And that’s because these have not started to acquire all the keratohyalin granules that we see in a much more mature basal cell carcinoma. These are just the basal cells. Typical pattern here is this large geographic island with the basaloid cells and also this characteristic clefting. And a lot of times, the tumors, in some cases, people will actually scrape these off and the tumor will pop right out and be able to separate away from the dermis. Just because they do not have a very good connection to the adjacent dermis with the tonofibrils and you see this characteristic clefting. But in other areas, you can see a very tight patterning with the desmoplastic stroma in between. It’s also worthy noting in here, you can even in basal cell carcinomas see a little bit of keratinization at times. It that does not make it squamous cell carcinoma, it’s still a basal cell carcinoma. Because you don’t see that normal level of maturation into the more mature-appearing squamous cells. On occasion, you do see these things where you’re kind of having a hard time deciding one of the two and some people would term these basal cells with squamous cell differentiation or they call them basal squamous cell carcinomas. But regardless, they’re both kind of in the same family here. Let’s go on to malignant melanoma briefly. Again, black highlighted because of the black pigmentation that we see in malignant melanomas. When you see something like this, this should raise the hair up on the back of your neck. You should be aware of it. A lot of different features that we’re seeing here, irregular different coloration and scalloped borders. Here’s another one, a very large lesion, very unnatural. Normally, in a lesion in any location of the body, everything is nice and smooth. This is very unusual geographic border. Another lesion here where we have some areas of hypopigmentation. And again, this lesion is irregular and non-symmetrical. Same type of thing here, the melanomas can look very, very different clinically and also microscopically pathologically. In here, we’ve got pigmentation and we got this pearly nodule here which is probably the vertical growth phase where this is starting to become much more significantly invasive, large neglected ulcerated malignant melanoma. Some of this is as probably the melanoma cells, other could be granulation tissue that’s mixed in with it. And then another prototypical malignant melanoma, irregular border and everything, we’ll come back to this here in a minute to talk about it. But let’s take a look at microscopically what this looks like. And what ends up happened is on malignant melanoma, the lesion arises at the dermal-epidermal interface which is where the epidermis meets the dermis. And that the basal cell zone, you start to have expansion of the melanocytes that are large and atypical. And ultimately, they first start off growing up which is a level one melanoma. But then they perforate through the basal membrane or I should say the basement membrane and they’ve extend it to the dermis, first the reticular dermis and filling the papillary dermis, then go in into the reticular dermis. And ultimately, extending into the subcutaneous tissue. Little high-powered, this shows what I was talking about before, we have these large atypical melanocytes present in variably-sized nest. Some of those extending up above the dermal-epidermal interface. Normal melanocytic nest will stay right nicely along the dermal-epidermal interface and they’ll extend into the dermis. When they start doing this, it’s called a buckshot pattern. And buckshot is bad in a gun and it’s also bad in the skin. To move along, makes a little higher power, that showing these large atypical melanocytes. And this is a special stain which is an immunologic stain which stains a certain component of the pigment component of the melanocytes. And so it just allows it to be able to highlight those and you could see all these little individual cells that are present up at all different levels, this buckshot pattern. That large nodular melanoma is a different specimen but you can see this. This is the same type of thing. We have this relatively sharp circumscription, ulceration on the surface. We’ve got pseudoepithelium and this hyperplasia where there’s this squamous epithelium is actually reactive to the melanoma here and then we go off to the normal skin here.

[20:00]

Little higher power just shows the normal but hyperplastic squamous epithelium and the melanoma here. Higher power identifies some of that pigment. And the pigment accumulation in here is very, very helpful. But it doesn’t always end up happening and you can have amelanotic melanomas, which are melanomas which are not even producing any pigment at all. And the highest power here shows this pattern of this relatively ugly cells, large nuclei, prominent eosinophilic nuclei, or prominent basophilic nuclei and there’s even mitotic activity, if I can see those. I think there’s one here and up here. So this is a bad lesion. This is, again, a nodular malignant melanoma. But that’s for a pathologist, we’re not pathologists here. I mean, I am and so we can talk about that. But I think the most important part about it is keeping you out of trouble in your offices. And so what you have to remember is clinically, how should you have a suspicion for malignant melanoma. And that’s the ABCs that have been put out for a long time. And so, just remember this in your office, you had A for asymmetry. This is where the lesion does not have a mirror-like configuration. Draw a line through a lesion and the right side should look a lot like the left side. The top should look like the bottom and it should be very symmetrical. You can see clearly, that’s not the case in this melanoma which we saw earlier. Second thing, border irregularity, and then what you want to take a look is you want to see if are the edges ragged, or notched, or blurred? In this case, you could see there’s an irregular notch there. I thought I had few errors, I apologize. But you get the regular notching here, and it’s not just a very natural looking lesion. It has a very asymmetric, geographic-type border. Next is the color. And in color, benign lesions typically will have a nice smooth uniform color. But in malignant melanoma, they’ll have non-uniform coloration and they could have black, brown, tan, all kinds of different colors with red, and white hues, and blues. And again, we can take a look at here, we have a large, very heavily pigmented lesion in the center and then a hypopigmented areas to the side. The diameter is important. When you’re looking at lesions, 6 millimeters appears to be about the area where you’re most worried about. Most of the benign lesions, not all, but most of the benign lesions are less than 6 millimeters. When they get above that level, that doesn’t necessarily mean that they are malignant, for things like cutaneous or I should say, a congenital lesion can be much, much larger. But, typically, we see a lesion that’s over 6 millimeters, you would raise suspicion. You can always remember that 6 millimeters is about the size of a pencil eraser. It’s an easy way to be able to remember that. Then, we have to remember the evolution is also an important component. When you have a lesion that’s changed in size, shape, configuration, it’s bleeding, it’s itching, it’s ulcerating, those are all very, very worrisome lesions or worrisome components that you need to worry about. So, let’s move on. You’ve taken it off. What should you expect in your pathology report? And I think the whole point of it is your pathology report should be there to be able to help you. It should be clear, concise and consistent. And when it’s coming out of a laboratory, it should be the same type of report with the same type of criteria, regardless with a pathologist A, B, or C reads it. If it’s coming out of the laboratory, it should have a level of consistency. Margin evaluation should be there when they’re appropriate. If it’s a basal cell or squamous cell and it’s excisional, they should have good evaluation for the presence of the adequacy of excision. And that’s also true in melanoma. Synaptic reportings are something that came off from the College of American Pathologists, and also we had been endorsed by the American College of Surgeons. It’s a standard set of criteria which should be reported in malignancies. And I’m happy to say that back in the early ‘90s, I was one of the original authors to help to see if we developed these in a variety of different tumor sites. And this is really, really important to be able to do that, to make sure that your oncologist who might be treating melanoma has all the information they need. Any kind of [indecipherable] [24:12] studies which should be done should be integrated in with that report and that makes it easier for you. And that you should ensure that the laboratory has proper accreditation. And the pathologists who are reading those materials have the licenses in the state that you’re from to make sure that they’re properly licensed. The thing that you should need to remember is the pathology report will help you see the hand that you have so that there’s no mysteries. In summary, I’m going to go quick. I’m almost to the end here. We talked about the top three cutaneous lesions to look for. You need to remember to look for the lesions. You have a high-ended suspicion and if you’re worried about something, biopsy it. Know what to biopsy and know how to biopsy that lesion, so that you know what you’re dealing with and not that you’re guessing on anything.

[25:02]

And when you do that, you’ll keep that ace in your pocket to keep yourself out of trouble. Again, I’d like to acknowledge where I got a lot of the images. I’d like to thank you for your time and attention. If there’s any other further questions, I’m out of the booth for the weekend. And again, thanks for everybody for their attention.