Working Up Cutaneous Squamous Cell Carcinoma: A Surgeon’s Perspective

[Dr. Gopi Shah]
When you think about-- when I think about risk factors, we talk about sun exposure, tanning beds, what other risk factors do these patients usually have?

[Dr. Gina Jefferson]
As you point out, UV exposure is the prime risk factor for the development of cutaneous squamous cell carcinoma. Age is certainly a risk factor. Typically cutaneous squame is diagnosed for patients that are in their mid-sixties, having fair skin. If you all recall the Fitzpatrick staging of skin fairness, the lower Fitzpatrick numbers are going to be of greater risk.

Then patients that are immunosuppressed. Primarily, if you think about a solid organ transplant recipient who are taking immunosuppressants, those patients will typically have on the order of 20 to upwards of 250 times the risk for cutaneous squame development in comparison to the general population. That increases with the number of immunosuppressants the patient is on. For example, a renal transplant patient, which is probably the more common transplant, recipients of a heart or lung are going to take more immunosuppressants. They're going to be at an even greater risk for the development of a cutaneous squame.

Other risk factors are having had a prior cutaneous squame, having had a burn injury of the skin, if you recall that. Then, of course, having had radiation treatment to the skin itself, all risk factors. There's another risk factor that's really important. Sorry. Patients that have a genetic predisposition, such as patients that have xeroderma pigmentosum or Muir-Torre syndrome are examples.

[Dr. Ashley Agan]
As far as thinking about the workup before patients see you, so for example, as a general ENT, if I see a patient and let's say I'm looking in the ear because they're there for hearing loss or something, sometimes I'll be like, "what's this on your ear here?" because it's very common to get things on the helix." I'll ask, "do you have a dermatologist? Has anyone seen this? How long has this been there?"

When I'm starting to think about if I should biopsy it, things that I think about are taking enough tissue to be able to make the diagnosis, but not enough to distort the area and have issues with margins if we come back. I feel like I need to leave a little bit so we know where the margin is. Can you speak to pitfalls or ways to tee patients up if it does turn out that it is a cutaneous squamous cell carcinoma so that we can send them to you with it appropriately worked up?

[Dr. Gina Jefferson]
That is a great question, Ashley. Obviously, you can have lesions of all different sizes. I typically see ginormous ones. If you are seeing someone with a really small lesion, it's going to be difficult for you to perform a punch biopsy and leave some residual behind to identify where it was located. In that instance, you would want to do an excisional biopsy with small margins on the order of three millimeters, achieve primary closure that will establish both a diagnosis, but also potentially and likely achieve cure of that small cutaneous squame.

It's the larger lesions or lesions near critical structures like the eye, like the nasal cavity, where you would perform a punch biopsy. The purpose of the punch is to assess the depth of the tumor because that is important in staging and how aggressive a cancer is. You would want to do the punch at an area of the thickest location, but you also want to obtain some normal adjacent tissue to allow your pathologist to truly assess the invasiveness of the disease to establish diagnosis. For the larger lesions, that is typically what I would do because the thickness, the depth of invasion is actually different than thickness. Yes, you want to assess that for staging the patient.

Typically you'll send a specimen in formalin and that basically fixes the cells in a state that preserves the architecture to allow the pathologist an accurate assessment. If you don't have access to formalin, certainly normal saline works.

[Dr. Ashley Agan]
Does it matter how big your punch biopsy is? You've got the little two or three millimeter and you've got the six or eight.

[Dr. Gina Jefferson]
Yes. I think our pathologists prefer four or five-millimeter punch biopsies to provide enough specimen for not only diagnosis, but the staining of the various immunohistochemical stains that they'll use is important when you are not certain that it's cutaneous squamous.

[Dr. Ashley Agan]
What's the role for Mohs surgery in these patients?

[Dr. Gina Jefferson]
I think Mohs surgery is actually a fantastic means by which dermatologists can treat the majority of skin cancers, non-melanoma skin cancers. What Mohs is, is surgical excision in a saucerized fashion. They're entering the skin at a 45-degree angle after they've removed the bulky exophytic component of the tumor. Basically, that saucerization technique enables the dermatopathologist to in real time assess 100% of the margin and then lay this out on a map so they can identify the area that might have positive margins still to only readdress at a subsequent excision only that area.

That means they're preserving as much normal tissue as possible and creating less deformity. The ability to assess 100% of the margins actually enables them to achieve good clear margins. That's so beneficial to the patient because there's no other technique that assesses 100% of the margin. Even when we do wide local excision, we're only doing slices of a sample of a specimen. All of the specimen margins are not examined. This enables them to achieve higher cure rates than wide local excision. Their cure rates are on the order of 3% five-year survival, disease-free survival versus on the order of 8% to 12% for wide local excision. I think that's an important adjunct to how non-melanoma skin cancers are treated.

[Dr. Gopi Shah]
When you have a patient that comes in and they've already had a biopsy and they come in with a path report, what are you looking for? What are some of the important characteristics that helps you with your decision-making in terms of treatment or outcomes or when you start counseling the patient?

[Dr. Gina Jefferson]
We always get the outside pathology slides to have our pathologist review and confirm the diagnosis. There have been occasions where the diagnosis has actually changed. I think that's really important. The features that we're looking for are the tumor differentiation. Poorly differentiated cutaneous squame are going to have a greater propensity for recurrence and regional metastatic disease than well-differentiated tumors. Looking for perineural invasion. Invasion of nerves greater than 0.1 millimeter diameter are important prognostically as well for recurrence. If the patient has undergone a curative surgical procedure, we're looking for the margin status.

What else are we looking for? Ulceration isn't really something that we are looking for with respect to staging for cutaneous squame. That's something that's important for melanoma. However, ulceration oftentimes will suggest that there is a deeper tumor and therefore more aggressive. We're looking for depth of invasion again. Any depth that's six millimeters or greater is highly concerning for the potential to spread to regional lymph nodes and beyond. Those are the key things that we're looking for. Of course, whether or not the diagnosis is truly cutaneous squame.

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[Dr. Gina Jefferson]
The mucosal squame actually does have a biomarker that's important for oropharyngeal mucosal disease. That's HPV. With respect to cutaneous diseases, probably know that Merkel cell has a virus that is specifically present in over 70% of those patients. Cutaneous squame does not have the same viral marker. It's been demonstrated that human papillomavirus may contribute to the development of, but not the maintenance of cutaneous squame. There's just no transcriptionally active human papillomavirus in cutaneous squame so that's why it's thought that it might predispose to the development of, but not maintain the progression of cutaneous squame.