BackTable / ENT / Podcast / Transcript #135

Podcast Transcript: Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction

with Dr. Gina Jefferson

In this episode of BackTable ENT, hosts Dr. Ashley Agan and Dr. Gopi Shah sit down with Dr. Gina Jefferson, professor and division chief of head and neck surgery at the University of Mississippi, to discuss the challenges of cutaneous squamous cell carcinoma (CSCC). You can read the full transcript below and listen to this episode here on BackTable.com.

(1) Risk Factors for Cutaneous Squamous Cell Carcinoma

(2) Physical Examination of Patients with Suspected Cutaneous Squamous Cell Carcinoma

(3) Obtaining & Assessing Skin Cancer Pathology Specimens

(4) Imaging for Cutaneous Squamous Cell Carcinoma

(5) Dealing with Positive Margins

(6) Addressing Neck Disease

(7) Planning for Reconstruction

(8) The Role of Radiation & Immunotherapy in Cutaneous Squamous Cell Carcinoma

(9) Surveillance Protocols for Cutaneous Squamous Cell Carcinoma

(10) Preventing Skin Cancer

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[Dr. Gopi Shah]
This week on the BackTable Podcast.

[Dr. Gina Jefferson]
Yes, thank God. Cutaneous squames, most of them are highly curable, do not metastasize, people live. I think it's of significant importance to pay attention to patients with two or more high-risk features to really evaluate them for the possibility of regional disease and certainly distant metastatic disease, particularly when they're a solid organ transplant patient. Just evaluate, evaluate, evaluate, and be attuned to that possibility.

[Dr. Ashley Agan]
Hi, everybody. Welcome to the BackTable ENT Podcast. We're a podcast that focuses on all things otolaryngology, and we've got a really great show for you today. Thanks for stopping by. Now, a quick word from our sponsor. Cook Medical's Otolaryngology/Head and Neck Surgery clinical specialty strives to provide otolaryngologists with minimally invasive solutions to address unmet needs. Areas of focus include head and neck, otology, and laryngology, with products ranging from a full suite of interventional sialendoscopy products and the Doppler Blood Flow Monitor System to the Biodesign Otologic Repair Graft and the Hercules 100 Transnasal Esophageal Balloon. For more information, visit cookmedical.com/otolaryngology. Now, back to the show.

We've got a great show today. My name is Ashley Agan. I'm a general ENT co-hosting today with the lovely Gopi Shah.

[Dr. Gopi Shah]
Hello, Ash. How are you?

[Dr. Ashley Agan]
I'm doing good. How are you?

[Dr. Gopi Shah]
Good. We have an awesome, awesome guest today. We have Dr. Gina Jefferson. She's a professor of otolaryngology and vice chair of education in the Department of Otolaryngology at the University of Mississippi. She's also the division chief of head and neck surgery, where she leads a team in surgical oncology and microvascular reconstruction. Dr. Jefferson is here to talk to us about the challenges of cutaneous squamous cell carcinoma. Welcome to the show, Gina. How are you? I am great. Thank you guys so much for having me. I'm excited to be here.

[Dr. Gopi Shah]
Gina, can you first start us off by just telling us a little bit about yourself and your practice?

[Dr. Gina Jefferson]
Sure. As you said, I'm a head and neck oncologic surgeon, and I perform microvascular reconstruction. One of my favorite things is cutaneous squamous cell carcinoma. We see a lot of them where I work in Mississippi. There's a lot of sun exposure in this rural state that I work in. I love the challenge of a complex reconstruction.

[Dr. Gopi Shah]
Awesome. Just jumping into how these patients are presenting to your office, are you usually seeing patients after they have been diagnosed since you are the tertiary subspecialist or do you ever come across somebody that just is in your office for something else and you're like, "hey, what's this?" I feel like that happens to me sometimes.

[Dr. Gina Jefferson]
Oh my gosh. That so infrequently actually happens to me. I think just being a head and neck surgical specialist, most of the time we're referred patients that have either been diagnosed and treated elsewhere, still have a management of their disease that needs to be addressed. There's the rare occasion where I've seen a patient and follow up for a mucosal site disease. They've come back recently.

For example, a patient came back with a cutaneous squame of the ear that was being radiated by his community radiation doctor. He'd gone through simulation and I was like, "Well, there's a couple of risk features here that are more than one in number. We probably should address this in another way." That's rare actually, because I do see the patients for surveillance regularly. Like I said, most of the time patients have already been diagnosed and or previously treated in an outside facility, whether it was by a dermatologist, a general surgeon, and sometimes plastic surgeons will address the primary disease as well.

(1) Risk Factors for Cutaneous Squamous Cell Carcinoma

[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.

(2) Physical Examination of Patients with Suspected Cutaneous Squamous Cell Carcinoma

[Dr. Ashley Agan]
For a physical exam, can you just walk us through if there are particular things about your exam that you are thinking of that's beyond what a normal head and neck exam would be?

[Dr. Gina Jefferson]
Physical exam is actually really important if you think about it, because it can actually clue you in to the degree of aggression that the tumor might be. Obviously, you want to consider size. That contributes to the tumor staging that we'll talk about. I think location is also important. Obviously, when you are thinking beyond the surgical resection, you're trying to consider how you're going to reconstruct. Obviously, if the primary site is in the periorbital area, for example, this is something that you're going to take greater consideration with how you're going to reconstruct so you don't impede the patient's lacrimal system, for example, or create lagophthalmos, which can become symptomatic.

I think one of the things that's really key is assessing the mobility of the lesion. If a tumor is highly invasive and involves underlying musculature, it's not going to be as mobile between your fingers. If you consider bimanual exam where you have one finger in the mouth, for example, and the other external on the skin of the cheek, you can feel the mobility. I had a patient that was referred after incomplete Mohs surgery because of the depth of invasion, which I think you can probably assess if you're considering that on your physical exam.

Another feature of physical exam that can clue you into the aggressiveness of the disease is whether or not the patient has nerve deficits, if they have paresthesias, if they have facial nerve that's out in one of the branches. That's another feature. Then, finally, with physical exam, it's important to assess lymph node status. People don't-- I guess a general surgeon or dermatologist might not recall or think frequently about the lymph nodes in the parotid glands because typically those are the first echelon nodes that are in the face. Palpation of the cheeks in the preauricular area where your parotid glands live, and then in the submental area, if you have a cutaneous squame that's lower third of the face, you might have lymph node development in the perifacial region over your mandible where the facial artery sits. Just examining the neck and the parotid glands is also of importance.

(3) Obtaining & Assessing Skin Cancer Pathology Specimens

[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.

[Dr. Gopi Shah]
In terms of diagnoses that haven't been confirmed squamous cell, is it that they've had like actinic keratosis or confused for in situ? What kinds of variations have you found in pathology?

[Dr. Gina Jefferson]
I think one of the things that outside pathologists sometimes have diagnosed are just the difference between the basal cell that has the squamous differentiation component and it might just be how the biopsy was performed. We obviously, don't know that because we weren't the diagnosing or biopsying provider.

Then the other instances in the event of a neck disease that's been diagnosed as metastatic disease, that diagnosis of determining if the neck squamous cell carcinoma is cutaneous in nature or mucosal is obviously, a challenge because there's no specific biomarker to tell you that this is in fact cutaneous squame. In those instances, you can perform next- generation sequencing to identify a signature of markers that lead you to think that it's cutaneous in nature in addition to other workup for PET scan and trying to identify the unknown primary site.

You would be surprised at the number of patients that come to you that are like, "Doc, I never had skin cancer before." You're like, "are you sure?" You’ll see on their face or other AKs, actinic keratoses, and you're just like, "I'm not sure about this," but based on prior or the scar location, it clues you into the possibility or likelihood that a patient probably did have a cutaneous squame in their past.

[Dr. Ashley Agan]
A cutaneous squame and a mucosal squame look the same under the microscope, essentially?

[Dr. Gina Jefferson]
Yes. There are features that-- the pathologist can perform some immunohistochemical markers that lead you down the path of cutaneous squame. They're not definitive.

[Dr. Gopi Shah]
For cutaneous squame, you mentioned that there's not specific biomarkers for mucosal and cutaneous squame, but are we looking at HPV stains? Are there other genetic type markers for specific to cutaneous squame or do we think of it like overall squamous cell carcinoma?

[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.

[Dr. Ashley Agan]
When patients come to see you, they already have a wound, a defect because someone has done Mohs and stopped, or they did a biopsy? Do they typically already have imaging? Do you prefer a particular type of imaging as far as CT, MRI, PET scan?

[Dr. Gina Jefferson]
I work in a practice where there's a facial plastic surgeon that predominantly works with the dermatology referrals for the Mohs defect. Obviously, there's occasion where Mohs has gone crazy with the number of layers that had been excised to the point where we have a full-thickness wound into the mouth, for example. Typically, my partner, the facial plastic surgeon will perform the reconstruction for Mohs.

What typically comes to us are those patients where my partner is like, "I cannot reconstruct that without a free flap," or typically it's a large squame where the anticipated defect is in fact going to necessitate more reconstruction than what's locally available. Then, of course, we frequently see patients that present with mets to the parotid gland that need to be addressed. Someone has treated the patient on the outside with excision but not considered the number of risk factors that would predispose the patient to development of regional disease, and the patient presents to us with regional disease.

[Dr. Ashley Agan]
For workup, does any size cutaneous squame need to have a further workup to evaluate for regional disease?

[Dr. Gina Jefferson]
Oh, yes. I'm sorry. I did not answer your question about imaging.

[Dr. Ashley Agan]
That's okay.

(4) Imaging for Cutaneous Squamous Cell Carcinoma

[Dr. Gina Jefferson]
Imaging is important. That is how we assess for what we call occult metastatic disease. If a patient doesn't have a visible lymph node or palpable lymph node, the imaging can pick up concerning lymph nodes greater than physical exam. Patients that are at risk, we consider patients that have two or more high-risk features such as size greater than two centimeters, depth of invasion six millimeters or more, whether it's occurring in a site that's already been treated for cutaneous squame, a site that's been previously radiated, and an immunocompromised patient. These are all increased risk features.

If there's two or more of those, then we're going to recommend assessment by imaging. That typically occurs by CT scan, or MRI, and/or PET scan. Immunocompromised patients with two or two or more of those features, I'm always going to get a PET scan. Then patients that have a recurrent disease, I'm also going to typically get a PET scan just because they're at greater risk for distant metastatic disease. People don't realize that cutaneous squame can kill you. That's by distant mets.

[Dr. Gopi Shah]
In terms of distant mets, what's the most common areas?

[Dr. Gina Jefferson]
Lung first and then obviously it can occur in liver, bone. Those would be the places to look. The PET scan will show concern for all of those locations all over the body.

[Dr. Ashley Agan]
Before we move on to management, anything else that happens for workup, like any labs or any sort of surgical planning stuff?

[Dr. Gina Jefferson]
Just typically the workup that you would do to ensure a patient's medically fit to undergo general anesthesia. Again, because these patients are typically diagnosed in their mid-60s, they probably have other medical problems. Patients are a lot of the time on blood thinners and they might not know why. Communicating with their primary doctor to make sure it's safe to temporarily suspend blood thinners for major surgery, those are the other type of evaluation that I would do for these patients.

(5) Dealing with Positive Margins

[Dr. Gopi Shah]
Let's say you have the patient, they come in with this defect. Let's say, the margins are positive. They're here to see you because the defect is big. We're still getting positive margins. How do you even start to think about-- how do you know where the margins were positive? Sometimes, it's hard the way the specimen may have been marked or the way the margins are set. The bigger the defect gets it's hard to know where to come back. How do you start to even, I don't know if the word map is correct, but orient yourself of where there might be tumor disease where we need to continue to excise?

[Dr. Gina Jefferson]
That's always a challenge when you're not the surgeon that's doing the primary resection. If I am doing the primary resection, it's easier to know where the margin's going to be positive for the skin. That does not hold true for the oral cavity, for example, where the 3D anatomy primarily of the tongue immediately changes upon excision. That doesn't hold true for the skin of the face. It's easier to mark your margins and you can go back and re-excise.

Now, the astute Mohs surgeon is going to provide the doctor to whom he refers a patient for positive margins, he's going to provide the map of where he has gotten positive margins and is just unable to clear the disease. In those instances, you will typically have a really good idea and ability to achieve margins. The problem is that oftentimes those locations are the eye. You're not trying to remove a patient's eye when the orbit itself, the globe itself is not involved. The mouth, when the lesion involves the cheek, you can go back and achieve margins and plan a reconstructive flap. The nose is also a little bit more complex. Generally, these locations, you can still do a wide re-excision and achieve clear margins without actually knowing precise location of the positive margin.

[Dr. Ashley Agan]
How many millimeters do you like for your margins?

[Dr. Ashley Agan]
The recommendations are about five millimeters. There have been studies, several studies, but I think there's one study out of UC Davis that demonstrated that there is a significant difference in disease survival if you achieve five-millimeter margins. We aim for that. Obviously in re-excision, it's hard to know that for certain, but your pathologist can tell you intraoperatively oftentimes in the area of concern where the positive margin was and the distance to the disease-free resection margin.

[Dr. Ashley Agan]
When you're doing your excision in the operating room, you excise the whole specimen and then you come back and take little slivers of margin to send individually? You've got the specimen, and you orient it, and then you take margins again, or you ask them to take margins off the specimen in real-time to give you an idea of if you're clear before you reconstruct?

[Dr. Gina Jefferson]
Yes. Typically, we take the margins from the specimen itself because that gives you the best idea of where the specimen is positive so that you can go back to that area if you need to. Cutaneous squame, it's possible to assess in real-time by frozen section examination? Yes. If you are able to achieve free surgical margins, then you can go ahead and reconstruct.

I think that's the approach of the Mohs surgeon. If they're achieving positive margins, they are not going to have the patient immediately be reconstructed by their facial plastic colleague. They will let them know that additional resection is needed and that it's probably going to require a more complex reconstruction than what they had originally predicted.

[Dr. Gopi Shah]
Do you have a system that you always use for how you mark or orient the specimen for yourself so you know where to go back when they start taking the margins off? What? Do you paint or do you—

[Dr. Ashley Agan]
I don't know, carve some little—

[Dr. Gopi Shah]
Yes, long stitch or a stitch? You know, “the long stitch is anterior towards the nose…”

[Dr. Gina Jefferson]
I usually will use marking, like a marking pen or paint. That just enables you to go back. The painting, that actually comes with a map in the kit so that you know the precise location as precisely as possible, obviously. That's helpful. I think the stitching is more helpful for orientation for the pathologist for the tongue, for example. A stitch per se for the face, probably not so much.

(6) Addressing Neck Disease

[Dr. Gopi Shah]
I guess pre-op you would have an idea whether or not you're going to address the neck or depending on where the primary site was that you're going to address the parotid. Once that specimen's off, you're going to go ahead and then start if you need to do the parotid or the neck at that time?

[Dr. Gina Jefferson]
The neck is of importance and can be addressed in a couple of different ways. For patients that don't have evidence of clinical disease, and you're not planning to do a flap, a free flap for reconstruction, you could consider doing a sentinel lymph node biopsy. This is not the standard of care by clinical trial. It is standard of care for melanoma. It's undergone multiple clinical trials. There are retrospective observational studies that demonstrate the high sensitivity of about 80%, the high negative predictive value over 95% for sentinel lymph node biopsy with cutaneous squame.

It's a viable means to assess the lymph nodes. It's going to be more sensitive than any imaging study because it's able to identify microscopic disease in the first echelon lymph nodes that you would anticipate by imaging from your lymphoscintigraphy. Everyone is not trained to do sentinel lymph node biopsy. The more frequently you perform sentinel lymph node biopsy, the more accurate it's going to be. That's one means of assessing the lymph nodes.

Then the other would be obviously, performing a neck dissection, which would include oftentimes for the head and neck addressing the parotid by superficial parotidectomy.

That would give you a pathologic diagnosis assessment of the lymph nodes. Patients undergoing a free flap, they're typically going to get a neck dissection simply because it gives you access to the blood vessels that you need to perform your reconstruction.

[Dr. Ashley Agan]
Patients who have, if we're thinking it's like a big T3, T4, big primary tumor, you are almost always thinking you need a neck dissection anyway, right?

[Dr. Gina Jefferson]
That's right. Even if they're not going to get a free flap. Very good. Yes.

[Dr. Ashley Agan]
The difference would be the inclusion of the superficial parotidectomy, because, in my mind, I'm thinking about mucosal squamous cell carcinoma, we're usually doing neck dissection. With the cutaneous, if it's on the scalp or on the face, the addition of the superficial parotidectomy is that extra site where it commonly goes.

[Dr. Gina Jefferson]
Primary site involving the upper two-thirds of the face, the forehead, the periorbital region, the cheek, the temporal scalp, those are all going to drain to the parotid before they get to the neck. That parotid requires assessment for sure and that's often where sentinel lymph node will also be located. The patient should be counseled to the potential need for superficial parotidectomy with sentinel lymph node biopsy. That's rare because typically you can obviously, take great care to identify the nerve out removing the entire parotid gland.

Then the lower third of the face, even the perinasal region, will drain partially to the parotid. Also, the lower third of the face, you want to think about perifacial lymph nodes that typically we don't address with mucosal squame, but perifacial and then submental and then of course level two.

(7) Planning for Reconstruction

[Dr. Gopi Shah]
When you start thinking about reconstruction. Tell me about-- you're smiling for those listeners, for the audience. Can you tell us a little bit about how you start thinking about reconstruction. I assume some of that thought process starts the minute you see the patient in clinic and maybe a plan A, a plan B, a plan C for once you’re in the OR?

[Dr. Gina Jefferson]
Yes. I think even when you are simply removing the parotid as the primary site with the overlying cutaneous squame over the parotid, you're always thinking about, can I close this locally without causing significant deformity? Particularly, you're thinking about the eye. You don't want to cause lagophthalmos. Also, you can also cause impairment of nasal breathing by distortion of the nasal vestibule with your reconstruction. Those things are first and foremost in your thought process.

Also, is this patient going to have exposed bone because when they're-- to me, they have already gotten advanced disease, so I know in my thought process they're going to undergo adjuvant radiation. If the bone is not protected well, it can lead to the terrible complication of osteoradionecrosis, which is not good for anyone. I think, in those instances, you're really considering whether or not complex tissue is more beneficial than just a simple skin graft. You're looking at the patient all over. You don't want to move a significant adjacent area that also has cutaneous disease, actinic keratosis, in situ disease. If you're just rearranging the potential of more cancer, that's also not the most helpful. You might consider full-thickness skin graft from somewhere else on the body that's not diseased. Whole host of things to consider.

[Dr. Ashley Agan]
That's a good point because the head and neck are going to have the most significant sun exposure over the years. If you're rearranging an area of skin that's just going to be the next cancer, it's good to go down to the torso or thigh or somewhere where that maybe hasn't had as much exposure over the years.

[Dr. Gina Jefferson]
Exactly.

[Dr. Ashley Agan]
As far as talking about the challenges of different reconstruction when you're having to, we can take this site by site, but you mentioned the eye a lot. Having skin cancer around your eye is really challenging. Can you unpack that more and dive into what you're thinking about when you're thinking about having to reconstruct that area?

[Dr. Gina Jefferson]
As far as the primary disease, you could have-- I've had patients with skin cancer in that sulcus between the eye and the nose. That one's challenging because of the lacrimal system. Do I need to stent the lacrimal system or somehow reroute it? Full-thickness eyelid, that requires reconstruction. Even for me, I will consult the oculoplastic surgeon to help participate in that reconstruction.

Then, of course, the more lateral you get, inferior lateral, I should say, any reconstruction is going to involve scar formation. Anything that's going to contract or pull the eyelid lower, that requires some kind of lateral canthoplasty to help prevent that. Again, I don't have any reservation in consulting my oculoplastic surgeon to help with that function and aesthetic appearance.

[Dr. Gopi Shah]
I think that's where the multidisciplinary and the partnership is very helpful.

[Dr. Gina Jefferson]
Love our colleagues of all specialties-- neurosurgery, ophthalmology.

[Dr. Ashley Agan]
For the noses, for example, sometimes if it's a significant portion of the nose, you may also be thinking about a prosthetic versus how good can I make it look with a free flap and some grafts because you're replacing cartilage, and giving it structure, and you need a mucosal lining. It's soft tissue and all these things versus having something that's a prosthetic, which has to be taken on and off. How do you think about those types of things?

[Dr. Gina Jefferson]
I think in my hands, I have done both ways of reconstructing before radiation, reconstructing after radiation. Either way, when you're dealing with partial or total rhinectomy, those patients are going to need radiation. Radiation is going to impact your reconstruction. It's probably better if you reconstruct after, but patients want something to just go out of the house. I think the best results aesthetically when you're dealing with a total rhinectomy are typically with a prosthetic nose.

I don't think it's obvious to patients that sometimes leaving a portion of the nose in those instances is less cosmetically pleasing than just simple removal of the entire nose because of the nasal subunits, just the ability to achieve the natural appearance, and contour, and the lighting impacts how you appear. The prosthetic nose in total is often a very reasonable means of achieving reconstruction, if you will.

When the full-thickness involves the nasal sidewall, for example, and/or the ala you can typically achieve some modest form of function as well as aesthetic appearance by flaps, the workhorse flap being the paramedian forehand flap with cartilage for recreation of the nasal ala. They can also reconstruct the strut of the nose if needed as well, the columellar strut. I think it all depends on the nasal defect, but when you're approaching subtotal, there's no such thing as subtotal rhinectomy. Just the entire nose probably should go when you're considering both resection as well as reconstruction.

[Dr. Ashley Agan]
It's complicated.

[Dr. Gina Jefferson]
It is complicated. The other thing that you should also know if you're going to have to create a common cavity between the skin and the underlying sinus or with the oral cavity, you're going to need three-dimensional complex tissue to help re-achieve, re-establish the barrier between the mucosal cavity and the external skin. That's where the free flap again is going to be warranted.

[Dr. Gopi Shah]
Tell me a little bit about the squamous cell carcinomas near the angle, on the lip. How do you tend to look at those?

[Dr. Gina Jefferson]
Funny you should ask. We just had a transplant patient whose entire head was cutaneous squamous. He needed a total auriculectomy, parotid, because he had mets to the parotid that were coming through the skin as well. He also had a synchronous primary of the lower lip, and it was not small. Literally, he needed a 20 by 15 centimeter free flap for the ear and then for the lip. Because of lack of other tissue, I did a Karapandzic flap.

I just think it depends on the extent of disease, the nature of the patient's available donor tissue. He's a small guy. The radial forearm was not going to provide enough tissue for his lower lip defect because it was three-quarters of his lower lip. His arm was very narrow. I was using an anterolateral thigh for the other defect, so it's just a lot of considering what other available sites a patient has to provide a reasonable reconstruction. You can do local fun flaps like the Abbe flap, Estlander flap for the commissure, the lip of it for Abbe. There's, obviously, a ladder for other lip defects.

Typically, my facial plastic surgeon will get those patients, but those are fun for the reconstructive surgeon who's usually doing ginormous recons, but I don't get them as much. I think if you're not considering the lip, you can also do less invasive recons like local tissue rearrangement, bilobed flaps, again, full-thickness skin graft. Those are all fun.

[Dr. Ashley Agan]
As far as your free flaps, is the ALT your most common workhorse free flap for the area or it just depends?

[Dr. Gina Jefferson]
I think it just depends. Depends on, again, the patient's body habitus. It also depends on the defect or the defect location. The ear and the parotid, it's a deep defect, but the scalp, for example, even the temple, you might consider a radial forearm because it's thinner. It's not going to be as bulky on the patient's head. If it's larger, you might need an anterior lateral thigh, but in most patients, the latissimus might become something that you consider because it's a thinner flap and won't be as bulky on top of the head. It's so many things to consider.

Body habitus should not be underestimated. I live in Mississippi, what that means is that even though they have cancer, they often are larger-sized patients, and so an anterolateral thigh might be thicker in a Mississippian than in someone that lives in New England, for example.

[Dr. Ashley Agan]
With the bulky flaps, do you tolerate extra bulk, let them get through their post-op XRT, and then say, “okay, we're going to come back later and maybe debulk this and make it more aesthetic, but for now we just will tolerate it being a little bulkier?"

[Dr. Gina Jefferson]
Oftentimes that's not even an issue even without radiation because the flaps aren't innervated. Typically, they are going to shrink at least 30%. Oftentimes, they shrink so much it's hard to imagine the size of the original flap. That's how much they shrink. It's pretty amazing. Sometimes if you're operating on the side, the lateral skull base, for example, if the flap is bulky enough where it's causing obstruction of lateral gaze, that's a time that I'll often reconstruct.

Even if the lower eyelid is appropriately suspended, they don't typically require revision or debulking. Debulking is rarely a necessity, but if it's obstructing some function of everyday living, then that's when we typically consider it.

[Dr. Ashley Agan]
How long does it take for it to shrink down, pretty quick?

[Dr. Gina Jefferson]
I wish I knew the true answer to that because everyone comes back for radiation and it's already shrunk. Sometime in that interim when I have not seen the patient, but even at-- I'll typically see a patient about six weeks after their surgical resection, and that's typically they've gotten simulated for radiation but they haven't started yet, it's shrunk some by then but it's typically not to the degree that I'll see when they come back. Around six weeks, there's already noticeable atrophy of the wound site.

(8) The Role of Radiation & Immunotherapy in Cutaneous Squamous Cell Carcinoma

[Dr. Gopi Shah]
Tell us a little bit about adjuvant when-- all these patients assume that the tumor board, and maybe they've come in with their pathology, the slides have been read with your pathologist and you've discussed them then, or perhaps it's post the resection and you're re-discussing. When do you start considering adjuvant radiation? The other question I had about radiation was, are there patients that get primary radiation for cutaneous squamous cell?

[Dr. Gina Jefferson]
I'll answer that one first because that's easier. Yes, there are patients that are medically unfit or who choose not to undergo the surgery that we've outlined for cure. They'll choose to have radiation as their primary treatment modality. It's often something that patients with cutaneous squamous of the nose will undergo because you can maintain the natural nose, and so yes, primary radiation is definitely considered.

Now, adjuvant radiation is beneficial for patients that have regional disease, and then stage 3 and 4 disease are typically going to get radiated. People that have positive margins are going to get radiated. Patients that have extra capsular extension with their nodal disease are going to get radiation with chemotherapy for both of those instances, and now about tumor board.

Cutaneous squamous cell, I should say, non-melanoma skin cancers are by far and away the most common cancers in the United States. They have risen over 200% in the last 20 years. Because of those vast numbers, tumor registries don't include cutaneous disease except melanoma for tumor registry. There's no tumor board for most of these skin cancers, but we have a tumor board for skin cancer for the reason that we see so many advanced cutaneous diseases. We will discuss anyone that is basically sent to the University of Mississippi.

Now, my facial plastics partner probably does not because he will get early-stage disease that contributes to those high numbers of patients that are just going to do well because 85% of cutaneous squamous, we're going to do well no matter how you treat them, whether it's medical treatment or surgery, but for that 15% that we're discussing with highly aggressive disease, those patients will typically get adjuvant radiation and then chemotherapy, positive margin, extracapsular spread, there is exciting developments with respect to immunotherapy.

In 2018 the FDA approved cemiplimab for recurrent disease, metastatic disease, not curable by surgery, not curable by radiation. People are able to achieve, typically, a partial response over 60% of the time, but there have been instances where people have had complete response. That's interesting. In 2020, KEYTRUDA was also approved for the same things as well as locally advanced cutaneous squamous, again, not curable by surgery or radiation, again, achieving high response rates partially and even complete.

Last year, a new study came out, a multi-center study using cemiplimab in the neoadjuvant setting, and patients were able to achieve complete response pathologically. Neoadjuvant, they underwent three to four cycles of cemiplimab and then they had surgery and over 50% of these people had a complete response pathologically. That is truly exciting. Ongoing clinical trials are obviously pertinent here to identify just what patients are best suited for those regimens, what the regimen actually should be, and then the duration, of course, durability, and the response that's achieved.

There have been high response rates for KEYTRUDA with respect to lung cancer, for example, in this setting. I think it's exciting to consider that patients might be able to avoid debilitating functional aesthetic surgeries.

[Dr. Gopi Shah]
Just to go back, sorry. Because some of these are used upfront, I think you said there was one where it was after five cycles of immunotherapy, then they had the resection, and they had high cure rate. Some of these can be used as initial to make the area smaller or just give us a higher response rate after surgery. Is that what we're saying, it's not just salvage, it's not just adjuvant, this is potentially a different way in our initial treatment options, this adds another tool?

[Dr. Gina Jefferson]
Yes, the question is, can you use immunotherapy to actually cure the disease without needing surgery? Because the study I was just mentioning, Neil Gross and colleagues, New England Journal of Medicine 2022, they looked at stage two through four cutaneous squamous and all of the stages had patients that actually had complete response pathologically, after they had surgery. Do they even need surgery? All questions that still need to be answered, but I think that's an exciting potential for immunotherapy. More remains to be elucidated on that front.

[Dr. Ashley Agan]
That means that when they looked at the specimen, there was no cancer in the specimen, right?

[Dr. Gina Jefferson]
Correct.

[Dr. Ashley Agan]
How do you know what to take? How did they know what to remove?

[Dr. Gina Jefferson]
Exactly. There was a lot of obviously photographic means to assess these patients. Typically as head and neck oncologists, we're trained that the original tumor dictates what you take after someone's had neoadjuvant therapy. Obviously in the head and neck, if you're trying to avoid removal of the eye, for example, this might be a means to adequately do that, achieve adequate disease-free survival and overall survival for these patients. We don't know that yet, but that's an exciting potential and remains to be determined.

[Dr. Ashley Agan]
For patients who are currently able to take immunotherapy, who, for example, were not a candidate for surgery or they had distance disease, are they on that indefinitely or at some point they're doing well and they don't have to take it anymore? How does that part work?

[Dr. Gina Jefferson]
Yes. Immunotherapy or in that sense is considered palliative, right, and so patients remain on that regimen with periodic imaging assessment to determine is the disease stable, is the disease regressing, or is the disease progressing? When patients development disease progression, typically the treatment is suspended. That's typically how immunotherapy or palliative chemotherapy even work and are supported by insurance so that you can be on it for an indefinite period of time. Typically it's about a year, but imaging generally occurs about every three or four cycles.

[Dr. Gopi Shah]
Which one do you tend to get? Is it a PET/CT scan?

[Dr. Gina Jefferson]
Typically a PET scan. There's RECIST criteria where they're criteria for the size or the volume of tumor on imaging. The PET/CT includes both the functional imaging, but also the anatomic imaging when you have the contrast.

[Dr. Gopi Shah]
Are these immunotherapies hard for the patients to take, or what side effects or what do patients when see them for follow-up and they're on it, what are some of the things they're going through?

[Dr. Gina Jefferson]
Typically diarrhea is one. That's one of the more common ones. Fatigue obviously is one. It can suppress the immune system to the degree where they have to temporarily suspend the immunotherapy dosing. Those are the most common ones. They don't typically cause hearing loss like platinum does when we're talking about adjuvant chemo/radiation. I think diarrhea is probably the one that most commonly occurs.

(9) Surveillance Protocols for Cutaneous Squamous Cell Carcinoma

[Dr. Gopi Shah]
In terms of surveillance, so I understand like that first year, if they're on immunotherapy after every couple of cycles you're going to get a PET. I would imagine, let's say they're not on immunotherapy, what is your surveillance? How do you like to survey your patients the first year or two out and then 5 and 10 years out?

[Dr. Gina Jefferson]
This is a very important question because over 75% of high risk cutaneous squamous is going to recur in that first two years, so they need regular surveillance. I will typically surveil my patients every four months, but I have strict recommendations to my patients. They have got to follow up with their dermatologist because that doctor is going to do the entire body skin survey.

If you have any kind of skin cancer, obviously your entire body has been exposed to UV radiation and is at risk. I'm only a doctor from the clavicles up. They have got to see a dermatologist. It's funny how patients, obviously, you know this, patients think that you're their doctor for everything. I'm like, "I do not treat hypertension. I'm not the one. I'm also not going to do your full body skin survey."

[Dr. Ashley Agan]
As they pull their pants down, "can you take a look at this?" "No." When you're seeing patients for surveillance, obviously you're looking at your the head and neck and looking at the skin and looking everywhere. Anything in particular that you-- is there a need for imaging later if there's no suspicion, or do you automatically get a CT at six months out? I guess it depends. You probably want to be maybe more aggressive with your immunocompromised patients or high risk.

[Dr. Gina Jefferson]
That is definitely sure for the high risk immunocompromised organ transplant patient. Definitely they get regular imaging. Now, patients that have regional disease, I also image their chest annually, just like I do for the mucosal disease sites. That's just because they have an increased risk for distant mets. The NCCN, the National Comprehensive Cancer Network guidelines do not include any of that.

This is just based on evidence that they're at increased risk for distant mets. The first place in distant mets is going to be the lung, so I will annually image that with a CT chest. The PET scan I will get for those organ transplant patients because of their ridiculously high risk of everything recurring locally, regionally, and distantly.

[Dr. Gopi Shah]
For the non-high-risk patients that had an extensive regional skin cancer that was resected, do you get a PET at the four month intervals initially, or is it just physical exam and maybe you get a PET at a year? What's the role of imaging for some of the non-high risk?

[Dr. Gina Jefferson]
The NCCN is actually not specific on type of imaging modality that you perform for any of the head and neck cancers. They just say image the chest. They even include in there chest x-ray, which we know is not as sensitive. My typical behavior is to get a baseline PET when all of the treatment is finished at the 10 to 12 week mark. Then if a patient develops concern for recurrent disease, you can repeat PET.

For those patients who have no evidence of recurring disease, I will, again, image the chest annually if they've had regional disease. Then, of course, as I said earlier, transplant patients are going to get regular imaging no matter concern on physical exam or not.

(10) Preventing Skin Cancer

[Dr. Ashley Agan]
Do you counsel them about sunscreen and wearing a hat and stuff like that or is it too late? By the time they're in their 60s and 70s and they've had all the sun exposure, is additional sunscreen and avoiding that, is that going to prevent them from developing another skin cancer?

[Dr. Gina Jefferson]
She said, "Is it too late?" Yes. In answer to your question, I counsel everyone in Mississippi on their wide brim hat, their sunscreen and to reapply their sunscreen when they're on their tractor mower or in the field farming. Now, whether or not it's protecting already sun damaged, condemned skin is another question, a good question, but they should be in the practice of preventing additional sun damage. I counsel them in this regard, and it sets a good example for those around them.

[Dr. Ashley Agan]
That's right. Any final pearls to leave our listeners with, or anything that we have missed or haven't touched on that you think is an important take home point?

[Dr. Gina Jefferson]
I think the important pearl is that, yes, thank God cutaneous squamous most of them are highly curable, do not metastasize, people live, but I think it's of significant importance to pay attention to patients with two or more high risk features to really evaluate them for the possibility of regional disease and certainly distant metastatic disease, particularly when they're a solid organ transplant patient. Just evaluate, evaluate, evaluate and be attuned to that possibility.

[Dr. Ashley Agan]
Thank you so much, Gina. I learned a ton. If our listeners want to reach out to you or get more information, are you on any social media?

[Dr. Gina Jefferson]
Yes. @drginajo on Instagram, YouTube and Linkedin. Same handle.

[Dr. Gopi Shah]
Well, thank you so much. I think it's a wrap.

[Dr. Gina Jefferson]
Thank you, guys. This was fun.

Podcast Contributors

Dr. Gina Jefferson

Dr. Gina Jefferson is a professor of otolaryngology and the chief division of head and neck oncologic and microvascular surgery at the University of Mississippi Medical Center in Jackson, Mississippi.

Dr. Ashley Agan

Dr. Ashley Agan is a practicing ENT and assistant professor at UT Southwestern Medical Center in Dallas, TX.

Dr. Gopi Shah

Dr. Gopi Shah is a practicing ENT at UT Southwestern Medical Center in Dallas, TX.

Cite This Podcast

BackTable, LLC (Producer). (2023, October 17). Ep. 135 – Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.