Stephen G. Ruby, FCAP, MBA, MD offers an overview of skin cancers: basal and squamous cell carcinomas and melanoma, including pathology, diagnosis and treatment. Dr Ruby includes case examples in his presentation.
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Stephen Ruby, MBA, MD
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Male Speaker: Speaker is Dr. Stephen Ruby who is a board-certified pathologist. He’s been in practice for over 35 years with laboratory experience. He’s a leader in the pathology field having served in leadership positions in a national state and local pathology societies. He is well published and he is going to be sharing thoughts with us today on squamous cell, basal cell and melanoma. So please welcome Dr. Stephen Ruby.
Dr. Stephen Ruby: Well good afternoon I’m the only person standing between you and lunch so we’re going to make this a little bit entertaining today. But I just want to say one thing real quick. Dr. Joseph, I enjoyed your talk. He and I are essentially contemporaries. I graduated in the 1981 and I’m going to just let you know what he said is spot on. Take away what he said there and really put it to heart. I only have one change on what he said. He was talking about how he thinks outside the box and I don’t really think that’s the case. When I hear what he’s done, this is an individual who doesn’t have a box. He’s clearly moved outside the realm of even to find himself as a box so you know what? Listen to what he has to say. Get involved in your societies and it’s going to make your career so much more rewarding. A lot of things used on – I had same experiences in my pathway and that’s really made this career so enjoyable. So again, with that I’m going to move on like I said. I’m only going to talk today about three things; squamous cell carcinoma, basal cell carcinoma and malignant melanoma and it’s Oh My. I’d like to mention real quickly, I make it a little bit of light of this just to make it entertaining but these are very serious topics and so we’re going to cover a lot of good information on here. But one thing I’d like to mention real quickly, if you take a look, I strategically put squamous cell in red, basal cell in blue and melanoma in black. And that was done for a reason because when we get to the histopathology, you’re going to see that squamous cells typically are more pink in color, basal cells have a much more blue color and melanoma has a much more black color. Part of this is done in fun but part of it is also is be able to give you visual clues. Let’s face it, you’re not pathologists. Most of you aren’t going to be looking down microscopes. It’s a field only some people like doing. But you’re going to need to know some of these things for your bores and for other reasons. For this reason, I’m giving you some kind of - basically fun ways of being able to remember this. So the question is who here has seen skin cancers either squamous cell, basal cell carcinoma or a melanoma? Who’s seen them? Okay. Who has not seen – who has not ever seen a basal cell, squamous cell or a melanoma? Because if you haven’t seen one yet, you will before the end of your career and you want to be able to detect those simply because it’s so critical for your patients to be able to – for you to identify those. Did you know that more than three and a half million new cases of skin cancer is diagnosed every year and there’s more skin cancer diagnosed than breast cancer, prostate cancer, lung and colon combined. So this is a big, big issue. Non-melanoma skin cancers have increased by 77% over these past years and 40 to 50% of Americans who live to age 65 will have a skin cancer of some sort. And you’re going to see these in your practice so you should become familiar with these. 2.8 million cases of basal cell carcinoma are seen, now granted most of those are probably on the face and that sun exposure is – but I’ve seen them also on the lower limb and foot. 700,000 cases of squamous cell. Those are probably more common in the foot than basal cells but you should be aware of those and those are big numbers, that’s annually. 65% of squamous cell carcinomas and 36% of basal cell carcinomas will arise in actinic keratosis or solar keratosis. These are lesions, preexisting skin lesions, precancers because of solar radiation or in some cases actinic radiation. And about 90% of non-melanoma skin cancers are associated with the UV light exposure. Also, from 1970 to 2009, melanoma has increased over eight times in women and four times in young men and a person dies from malignant melanoma just about every hour in the United States. Melanoma makes up less than 5% if skin cancers but it’s the majority of cancers which produce skin cancer related deaths. And 1 in 50 individuals will be diagnosed with malignant melanoma in their lifetime and melanoma is only one of three cancers in men which has an increase in mortality. It’s important to remember, for melanoma, the five year survival of it caught early is 98%.
If you catch it a little bit later once there is regional lymph node metastasis, that five year survival drops to 62%. And if it goes a little longer and it becomes distant organ metastasis, that drops to 15%. Now in melanoma, the change of going from an early lesion to distant organ metastasis is measured in millimeters of thickness on the lesion. So it’s very important that you detect these lesions as soon as possible and one of the reasons for that is because a failure to diagnose melanoma is probably one of the major malpractice risk that we have. So the question you say, did you guess it, the diagnosis if you saw something clinically on your foot or did you document it? I’m sorry, or did you document it? And at this point, I’d like to introduce myself again. I’m Dr. Stephen Ruby. These are not my shoes but they’re the closest I could find that they’re closest to ruby slippers as we’re looking at The Wizard of Oz theme here. I am a Medical Director and the founder of 4path Laboratory which is a pathology laboratory which has a specialty area in Podiatry. We’re – I’m in the Chicago suburbs and obviously, our local here. Objectives of the lecture today will be to understand the three most common forms of skin cancer that we’re seeing and dealing with. To understand a little bit about tumor histogenesis. Where do these tumors come from within the skin? What’s the role of biopsy technique and the importance of biopsy technique in these different types of cancers? What to expect in a pathology report and last but not least, learn how to stay out of trouble when you’re dealing with skin lesions. Next thing I need to do is just quickly describe that I have a laboratory. I obviously do work and drive my income from that but I don’t have any other types of financial disclosures to disclose at this point in time. So let’s kind of jump into things here and say where do skin tumors originate? And when we take a look at it, the three major skin lesions that we’re looking at: the squamous cell, basal cell and melanoma all arise in that small little thing area that’s at the top of what we call skin, okay? The squamous cells are the more superficial component that has been mature. The basal cells are also squamous cells but what ends up happening is that basal cell component hasn’t shown the maturation and they behave differently and then melanocytes are the origin cell of malignant melanoma. But we can’t forget that there’s also other kinds of skin tumors including skin adnexal tumors and this could be tumors that are rising from hair follicles, sweat glands, sebaceous glands. We can have connective tissue lesions that are arising from the other components of the dermis such as smooth muscle tumors arising in the erector muscles. In the hair or actually in the walls of the blood vessels. And then there can also be infiltration of leukemia lymphoma and I didn’t even mention metastatic lesions here because that’s not a primary tumor but yes, you’ll always have to remember about metastatic lesions and the good part about doing systemic pathology in addition to skin pathology is we see all kinds of breast cancer, prostate cancer, lung cancer, everything else like that on a regular basis so when it presents itself in the skin, it’s not – does not present with a confusing picture because we’re used to seeing it at the other sites of origin.
So how should you tell the different types of lesions apart? Should you just use your clinical judgement alone and treat based upon that or should you use clinical judgement and biopsy? And my obvious bias is that you should be biopsy but the question is why should you biopsy? And first of all, it’s to establish that diagnosis so you know exactly what you’re dealing with, okay? And that diagnosis is going to help you better develop your treatment plan and follow it for the patient. And the other thing is – what people always forget is that the pathology report can provide you with a level of, if you will, practice insurance. A lot of people don’t like talking about this but it’s really true. And I’d like to give just a quick little – a little scenario here and that is – let’s say that you’re seeing a patient and they’ve got a benign lesion, a benign verruca on the foot and you’ve decided – and you’ve seen thousands and thousands so you know what it is, it’s a verruca so you decide to burn it off or treat it somehow but you never biopsy it. Now let’s say the same individual has a perianal melanoma or some type of maybe internal visceral melanoma, okay? Not related at all to the foot lesion and they end up developing metastasis in the groin. So what ends up happening is, the patient gets diagnosed with metastatic malignant melanoma. Well the first thing they do, first question that any kind of shall I say, plaintiff attorney would say, “Okay well, did you ever had anything taken off?” They’ll say, “Well yeah. I had something taken off my foot by Dr. Joe Blow a couple months ago or maybe a couple of years ago.”
So they’ll come knocking on your door and say, “Can we see the pathology report? Why – what was it that you took off?” You say, “Well, no, it was just a verruca. I know what it was. I just burned it off.” You just might as well write the check right then and there because the point is if the patient has an established diagnosis of metastatic lesion and the smoking gun is going to be pointing at that lesion, whether or not it was and in this it wasn’t, okay? And they may never find the original site of origin because these lesions are so small. But if that person comes knocking on your door and says, “Well what about that lesion?” You pull out a report and you say, “it’s a – that was a verruca and we proved it histologically. You’re now scot-free. In other words, you have evidence to prove why you did it and that there wasn’t a cause of the metastatic melanoma. So remember, it’s an important insurance policy for you and your practice and trust me, you don’t want to go through the process of having to defend a situation which really didn’t need to even occur. So let’s talk about excisional versus incisional biopsies and obviously, the first one is the excisional biopsy and this really for – this really provides two major benefits. It provides the diagnosis and in many cases it can be therapeutic and if you have a complete excision of the lesion. The other is the incisional biopsy which is pretty much limited to a diagnosis only and it – when we move on in here I want to be able to just really – I want to say it now so I don’t forget to say it later. An excisional biopsy, if you can take something off in total, it’s never a bad thing. If you could do a primary closure, take care of it, it’s fine. You can always do that. For an incisional biopsy, in other words, one that’s for diagnosis only, that’s probably reasonable for a squamous cell and a basal cell carcinoma but as a matter of fact, I had a conversation with a resident earlier this morning. He was asking me about incisional biopsies on melanoma and I said, “Really, you should never do an incisional biopsy on a melanoma. It should always be an excisional biopsy on a melanoma.” Now you might get the margins very thin, very close but you should always make sure that you’ve got as much as you can on the entire lesion and the full depth of the lesion because you’ve only got one shot to be able to get that thing out intact and be able to do all the stage and the depths and the thickness of the lesion. So you should – on melanomas, you should always excise those completely unless there’s a very, very good reason why you always only should do an incisional biopsy. Perhaps it’s so large that you’re just trying to establish a diagnosis but in most cases, when you’re dealing with a smaller lesion, excisional biopsy is the way to go for melanoma. So let’s take a look at some different pictures of cancer. Obviously, if I was in a pathology meeting, I would have already probably put you to sleep with about 30 pictures but we’re going to keep this short and light. Basal cell carcinoma clinically, nice. Relatively round, well circumscribed. Rolled, curly borders and a nice ulcerated area. This is a nodular basal cell carcinoma. Obviously, it’s elevated and we’ll take a look at that in a little bit. This is probably a superficial multifocal basal cell carcinoma but you do have some nodular areas on it. It has a pearly appearance. Sometimes they’ll ulcerate a little bit. There’ll be erythematous and sometimes it’s very hard to tell the edges on where the lesion begins and where it stops. On this one, if you’re excising this, you can feel pretty confident about where you’re at but on a superficial multifocal ones they just kind of trail on and on and on and on. And I’ve seen these cases where people have gone – they take a slice, take a slice, take a slice and we’re doing frozen, after frozen, after frozen. And in all reality, most likely, these would probably be treated with a different form of treatment than just pure excision. Here’s another basal cell carcinoma. Again, the rolled borders. A little bit of pearly appearance and some ulceration. So what does this thing look like microscopically and we could see we have nice geographic islands of those blue basophilic cells, okay? So that’s why the basal cells always been in the blue color. The arise from the basal zone on the epidermis and then they grow downward. They have a lot of fibrosis and there’s a very tight relationship in this type of basal cell carcinoma between these dark islands and the fibrosis that’s in the dermis. The other characteristic of basal cell carcinoma and this is nod – more of a nodular – the other ones are nodular pattern but this is more of a typical nodular pattern. You have these large islands and this confluent growth of these basal cells. And again, it’s all very, very blue. But this is a characteristic finding, this clefting away from the adjacent soft tissue and that’s a very, very characteristic. A lot of times you’ll also see it dipping down from the under surface of the epidermis. And we didn’t – then I didn’t mention it before because I was assuming that you had a relative basic concept of histology but let’s just talk about it real quickly here.
When I mentioned that the tumors that we’re talking about, the top three. They’re all arising from this little part of the epidermis. Not from the dermis in deeper tissues but over here. The basal cells are coming off of this basal cell zone here. The squamous cells do have some levels of maturation and go up there and that’s why they change their appearance and the melanocytes are also along here but they’re a different cell population. So going on, this is just a little higher picture of the basaloid islands in here, the dense fibrous connective tissue and another interesting part is, on occasion, basal cells can keratinize a little bit so just because you see keratin, doesn’t always mean that it’s not – that it’s a squamous cell carcinoma, that it’s not a basal cell. Some basal cells can keratinize a little bit especially when they become ulcerated. The whole surface can keratinize a little bit microscopically. So one thing to remember, again going back to our theme basal cell carcinoma are like the foot soldiers. They march around a lot, they can do a lot of destruction locally but they can’t fly. They rarely, rarely, rarely metastasize, okay? So let’s move onto squamous carcinoma. This is the red lesion here and let’s go clinically, obviously, it’s a lot different appearance. We got a large chronic area of injury. You’ve got a large irregular ulceration. That rolled border, that clear demarcation is just not there. It’s much more rag in its appearance. Here’s one that’s right around on the lip. Again, sun damaged skin, you got the actinic cheilitis which is sun damage on the lip. And this can be fooled into possibly thinking that it’s a basal cell carcinoma incision and biopsy is going to be able to help you figure that one out. Let’s go on, this is actually the foot with the toe is evolved by squamous cell carcinoma in situ and some invasive squamous cell carcinoma and chronic radio radiodermatitis. So again, rather than being solar keratosis which is damage from UV – radiation from the sun. This is actinic keratosis which is – radiation which is artificially produced. We’ve got another picture, same type of thing. You’ve got that ulceration, loss of the nail. And the other thing to remember with squamous cell carcinoma is this is actually between the toes and this is a chronic verruca and the verruca in this case has degenerated because of chronic irritation and changes into an invasive squamous cell carcinoma. Remember, the verruca is a viralation and you can have inclusion of that viral genome into the native DNA or into the native DNA content of the cells and then degraded into a squamous cell carcinoma. So let’s look microscopically. You can see again, that more pink color. Large geographic islands and they’re much more variable in size, shape and configuration. In here, although these basal components look a little bit like the basal cell carcinoma, you can see we do have maturation and these large geographic islands of keratinizing cells. And you don’t have that characteristic clefting so it is significantly different appearance than you would see in a basal cell carcinoma but having said that, there are times when you could have a differentiation though that some physicians will use the term of basal squamous cell carcinoma or keratinizing – well not a keratinizing basal cell but – because that’s – we pointed out before actually a basal cell but there can be a little bit confused but most of the time it’s pretty straight forward. Little higher power, just showing those basal or the squamous cells with the significant pleomorphism. There’s some large nuclei atypia. Little higher power, showing the keratinization, some hemorrhage and even more of a pleomorphism in large cells, a regular nuclei and again, just a little bit more just to be able to see it, individual cell keratinization. So they really do look a lot different than just a basal cell carcinoma and the important part in squamous cell carcinoma is to remember they can be little – they can be little mean buggers and it’s hard to predict them. Because in addition to being invasive, okay, invasive and locally destructive, they can sometimes fly. And even – and sometimes in small lesions they can metastasize to regional lymph nodes. So again, basal cells are more marching. They stay localized and the squamous cells kind of occasionally, sometimes fly and become metastatic. So everything seems pretty good. We’re down the yellow brick road. Everything – we’re getting a pretty good idea of what’s going on but what we forget, there’s one more lesion of the top three that we talked about and this is one that we have to worry about. And this is probably the one that’s most feared by individuals and I’ve got a variety of different pictures here where you can see that we have a lesion that has an irregular border, small and macular. Here’s one with a nice pearly nodule on it. Another one with a very irregular geographic border and a dark coloration.
Same type of thing with a little – oops. With a little area of potential regression and pink discoloration there. Here’s this person on their back with not one but actually two lesions which is not unusual to occur, multiplicity. This – one with a regular borders and some elevation and nodularity and another which is very large, neglected and ulcerated and this is malignant melanoma. This is the one you really – you really want to worry about in its early detection is so, so important. When they get to this point, your patients got a lot of problems. And you have to remember that just like the Wicked Witch of the West, these are really mean little lesions and even though they can be small and petite like the witch, they can really pack a punch when it comes to trouble. So let’s take a look microscopically on malignant melanoma and what we have is a lesion that often – well if it starts right at the dermal epidermal interface. So it starts from the cells, the melanocytes that are present at this DE junction and they start to proliferate become atypical and abnormal. When it’s at this phase moving here right along the epidermal dermal – dermal epidermal junction, that’s a superficial spreading malignant melanoma but when they create a large nodule that’s extending down. That’s considered vertical growth phase which is associated with the deeper levels of invasion. So let’s go a little higher power, same type of thing here. Here’s the epidermis that we’re seeing with the squamous cells and the basal cells but we’re seeing these clusters of atypical melanocytes that are present in all levels of the epidermis. They’re large, they’re irregular, they’re not naturally curved like the – like a nice ball configuration. The cells done have the normal level of maturation and orientation that you’d normally see and in here, this is a level one melanoma but then once it gets into the dermis, then you start going into this level two, three, four and five melanomas. And again, this is a nice high power to show you on a – an irregular nest. These are large atypical cells prominent nucleoli. Even individual cells that are up in the epidermis. This is called – this is what you call the buckshot pattern that you’ll hear people talk about or sometimes – there’s a variety of other terms but I like the term buckshot pattern because it really is very descriptive that you see these melanocytes, these atypical malignant melanocytes at all levels of the epidermis both individually in a large nests. This is a special stain, it’s Melan-A and it highlights and paints the melanocytes, the atypical melanocytes and the reason I put this in is number one, to show you how large and irregular these melanocytes nests are. Actually, this is the same lesion as we just saw before and also, you can see all of these variably sized melanocytes at all levels of the epidermis. Now that was – were mostly, mostly what you would consider as a superficial spreading but then we go into the nodular or the vertical growth phase melanomas and I have the edge here. This is a lesion which we can see the edge is right here. This is normal epidermis here, normal dermis and then all of a sudden we got this hyperplastic change and this hyperplastic change of the epidermis is probably because of the ulceration here. And – but we have this large nodular melanoma here and these are all atypical melanocytes involving the dermis and extending into the dermis and the surface is ulcerated. Little higher power just to show you the same thing. Not always having that epidermal change as we talked about before and the reason for that is this is undermining that epidermis. It’s marching out to the side and is undermining epidermis so sometimes you won’t – might not see that and if it – that surface part where it originated is ulcerated, it might be gone completely. Little big higher power, same type of thing here but now we start to see that dark pigmentation and we see some of these buckshot melanocytes present up in the epidermis. We see that the extension and the confluence of the malignant melanoma cells in the – in the dermis, a little high power there and you can even see some myotonic activities, some pigment in these cells and again, this is just a confluent component in a vertical growth phase of melanoma. So having said that, how did – what do you need to do to be able to evaluate pigmented lesions and it used to be that you’d say that A, B, C is the melanoma but actually it’s become the A, B, C, D, E and I’m waiting for somebody to come out with the F of melanoma and – so let’s take a look at this lesion and start off and let’s apply these A, B, C, D, Es to it. First of all, the asymmetry. In a lesion, when you’re evaluating it clinically, place a line through the center of it in any direction and it should most of the time be pretty symmetrical and you can see in this case, it’s not symmetrical at all. The left side looks entirely different than the right side. The second thing is we take a look at is the border of irregularity. In benign lesions, the borders are typically much more smooth, round and even. It’s kind of – if someone called it a natural appearing border. In other words, not an unnatural border.
Now that’s not to say that a melanoma can’t have a nice natural border, but more likely when you see those kinds of changes then what you want to do is start -- you know, like the hair on the back of your neck should stand up. The next thing is, is we talk about the color. We can see a lighter color here but then we go and look over here, you got this dark coloration. Variation is something that you should also look at clinically and when you’re seeing that kind of thing, okay, still getting the hair on the back of your neck should stand up and then start to worry about it being a malignant melanoma. And then the next thing on top of it is, you can use a pencil. The tip of the pencil is about six millimeters and lesions that are below six millimeters, they’re not always benign but it’s a good marker that says if things are bigger than six millimeters or that tip of that pencil. Start to think much more critically about the possibility of this being a malignant melanoma. And then the last thing is – last thing also is the evolution of the lesion. When you’re starting to see lesions that change color, they grow in size, they have small satellite lesions. They’re creating a nodule. They’re starting to itch or bleed. All those things again, highlight the possibility of this being a malignant melanoma. So hopefully these pieces of information when you’re looking at somebody clinically will make you see this lesion and say, “This thing needs to come off and be examined microscopically.” So we’re all pretty happy now. We’ve pretty much figured that we’ve got a good handle on squamous cell carcinoma, basal cell carcinoma and malignant melanoma so the question that we should ask is, when it – the lesion is sent to the pathologist, what should you be looking for in a report? And it's more than just a – oh actually, I’ll put it on here because I don’t want you to blow your top over having a bad report, okay? So the point is, is first of all, your report should have a diagnosis and part of the diagnosis should be a nice microscopic description. Some laboratories put those in, some laboratories don’t but you should have a gross description describing what the lesion looks like grossly for documentation. And then a diagnosis which is clear in an unambiguous and has all the information that you need in it. The – when you’re doing an excisional biopsy or a – for that matter even sometimes in an incisional biopsy, they should clearly state where the lesion’s been excised or not. And what are the margins look like? Are they – are the margins free of lesion or are you – do you have involvement of the margins? And if possible, okay, and one of the things we do routinely is we use four color inks. If you provide a stitch at the 12 o’clock margin, we usually do four color inks and give you which margins involved. 12 to 3, 3 to 6, 6 with 9 and 9 with 12 or the deep margins. So it helps you if you have to go back and do a re-excision but – but that’s an important component. Next thing is, is synoptic information. Synoptic information is actually a whole compendium of very important information especially in malignant melanoma to be able to help establish your – the treatment protocols and what people need to do for the oncologist and such. And these have been established by the College of American Pathologists. This is actually a committee that I’ve – well I’ve done it on other sites but not for melanoma but the College of American Pathologists put together with the American College of Surgeons and – so it’s a nice standardized components that you should have on those reports especially for malignant melanoma. And then the last thing, if there’s any kind of ancillary studies flow cytometry, if it’s a lymphoid lesion or sometimes there’s also molecular studies. Those should be all incorporated into the report. So with that, let’s wrap things up. We’ve talked about the three biggy lesions, the most common ones. Squamous cell, basal cell and malignant melanoma. It’s important that you look for the lesions. You won’t see them if you don’t look for them so you look at the legs. You look between the toes. You look at the nails to see it. And you’re not going to see a melanoma that’s underneath the nail if the patients got nail polish on it. You just aren’t going to see it. So you got to remember, if you don’t look, you’re not going to find it. But you’ll probably still be responsible for it. Have a high index of suspicion when you’re looking at these lesions and question it. The question you should always ask, “Is this something that I need to worry about in biopsy?” And so that’ll lead you into the next thing is, “What do I need to biopsy?” and, “How do I want to biopsy this?” Important part is have a good rapport with your pathologist because they’re the person that’s going to be able to help answers all the questions that you have about this and subsequently, with – if it requires more treatment by the oncologist. They’re going to have to be able to refer to them and talk with them so have good rapport with your pathologist and with that you’re going to be welcome to the world of Oz where all your diagnosis are correct and I hope that everybody here in their entire practice, in their entire career will always – always get the right diagnosis on everything. I know that’s probably wishful thinking but let’s hope that in the vast, vast majority are. I would just like to do a quick acknowledgement of the images that we took especially the clinical images were from dermis.net and I’d like to thank you for your attention because lunch is right around the border – right around the corner after and I really want to appreciate your – I really appreciate your attention through this period of time because I know everybody’s hungry and with that, I’m going to conclude with 40 seconds to spare. Thank you everybody.