Glenn J. Hanna, MD: We’ll jump into cutaneous SCC [squamous cell carcinoma], which is a more prominent issue in our clinics, given the prevalence and incidence of the disease. We’ll turn it back to Dr Emerick, our surgeon, and talk about the frequency at which he’s seeing cutaneous SCC, particularly in his head and neck oncology clinic. Maybe review for us some of the things you think about in regard to immunosuppression and risk factors and how you begin the process of staging patients and formulating the diagnosis.

Kevin Emerick, MD: Thanks, Glenn. We’re seeing a lot of these patients. They come in a few different forms. They come in the form of your primary tumors that are bad actors, as well as regional metastasis. Occasionally, metastasis is how they’re showing up. When you think about having around a million squamous cells a year, most of them are not bad actors. They’re all very well behaved. But if you start thinking about it, even 10% of a million starts to be a pretty big number. Think about 20% of those life-threatening tumors, and this is still a real issue.

In my practice, I see a lot of what we might consider to be high-risk primary tumors. High risk is really a generic term—it means different things to different people—but we can think about high risk of coming back someday in that same location or a high risk of spreading to the lymph node, a high risk of spreading somewhere else in the body. One of the problems with squamous cell carcinoma, when you have a million cases a year, it becomes hard to know the important prognostic factors to clue you in and say, “Hey, worry about this 1.” Nonetheless, we can talk about what we do know.

Size again is important with basal cell. We started thinking about tumors that are bigger than 2 cm. We start thinking about poorly differentiated tumors. Tumors that deeply invade, whether that’s a measurement of 6 mm or into deep soft tissues, such as muscle fascia or cartilage and bone. Those are some real basic things that we should be thinking about, also perineural spread and lymphovascular spread. These are important things you might start to see on path reports that might clue you in.

There are lots of other clinical clues. One that’s obvious is the tumor that comes back again. It’s been treated, they’ve had Mohs [surgery], and they’ve had excision, and it comes back even if they said it was well differentiated. A tumor that comes back is not good. Some other stuff has been harder to quantify, but tumors that grow quickly tend to be bad actors. Tumors that are symptomatic, meaning they’re painful. Tumors that invade into nerves and cause symptoms or some of those features. And maybe the big 1 becomes immunosuppression. We know that our immunocompromised population is important. The obvious 1 is our solid organ transplant population. I’ll focus there, but we shouldn’t forget about all our other patients on steroids or on other immune modulators for their psoriatic arthritis, for all of the other things our rheumatologists are doing an amazing job treating. We haven’t studied that. We don’t know that impact, but I’m sure it’s important. And we’ve seen that in our practices.

Solid organ transplant patients have somewhere between a 65 and a 250 times risk of getting a squamous cell carcinoma and probably are 50 times higher risk of getting multiple squamous cell carcinomas and a much higher—maybe a 13% higher—chance of having recurrent squamous cell carcinoma. When a patient who has a solid organ transplant walks in the door, you perk up your ears, especially if they have any of those other risk factors I was just talking about.

When I see primary tumors, those are the things I start to think about. When we see regionally metastatic tumors, we want to clinically look at those tumors. You think about the carotid. That’s the most common site of metastasis within the head and neck. When we think about the carotid, we think about the facial nerve. We think about the ear. As this tumor is growing, is it invading into those nerves? Is it invading into the ear? Does it have perineural spread into the ear? And we need to distinguish between direct envision and perineural. Those are the things I started thinking about in terms of lymph nodes and the product. How big are they? Is this a 1-cm lymph, or is this a 4-cm lymph? Are there 3 or 4 of them? Those become some of the initial things of the folks that I see.

Part of your question was, how do we take that? As oncologists, we all say, how do we stage them? How do we take that risk and put it into a staging category? There are 2 important staging categories people need to be aware of. One is AJCC [American Joint Committee on Cancer]. For oncologists, that’s what we’ve always used. That’s what we’re familiar with. But we like AJCC because it thinks about the primary tumor, but it thinks about lymph nodes and about distant metastasis and puts all that together. The problem is we’ve never had amazing data to inform AJCC staging, such that after AJCC 7, they wanted to do away with it. And it was the head-and-neck group that was part of AJCC that said, “We still need this.” You’ll notice that in the AJCC 8, the cutaneous squamous cell and basal cell speaks only to head and neck. I’m sure it’s translatable to other sites, but the data are being used. One of the challenges of that staging system is that it oftentimes focuses on size and only 1 risk factor, like 1 size feature or 1 deep invasion perineural spread.

I also think about, for those primary tumors, the Brigham and Women’s Hospital staging system, which focuses on 4 risk factors. For those primary tumors, create a risk profile to think about the risk of regional metastasis. Those 4 features become size greater than 2 cm perineural spread, poor differentiation, and deep invasion. Deep invasion, meaning beyond the subcutaneous fat or greater than 6 mm in size. That becomes my starting point in terms of thinking about some of the epidemiology of these patients and those initial prognostic factors. And then we try to wrap that into a staging. We try to use both of those staging protocols to guide the treatment for these folks.

This transcript has been edited for clarity.