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

Author Julia Casazza covers Working Up Cutaneous Squamous Cell Carcinoma: A Surgeon’s Perspective on BackTable ENT

Julia Casazza • Feb 2, 2024 • 32 hits

Non-melanoma skin cancer (NMSC) – a category that includes cutaneous squamous cell carcinoma (SCC) – represents the most common type of cancer in the United States. Rates of NMSC continue to climb, with case numbers up 200% in the past two decades. Though smaller SCCs can be treated by dermatologists, lesions that are larger, clinically advanced, or located near critical structures should be evaluated by a head and neck surgeon. Dr. Gina Jefferson, a head and neck surgeon who runs a busy cutaneous SCC practice at the University of Mississippi, recently joined BackTable ENT to share her pearls on how to evaluate this disease.

This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable ENT Brief

• Risk factors for cutaneous squamous cell carcinoma include age, fair skin (lower number Fitzpatrick type), prior history of SCCs, burn injuries, radiation treatment, and immunosuppression.

• Physical examination of the patient with suspected SCC requires assessment of regional lymph nodes. Lesion location and characteristics (e.g. mobility) should be noted.

• Pathology is required for an SCC diagnosis. In the case of smaller lesions, excisional biopsy can be both diagnostic and curative. For larger lesions, clinicians should obtain samples using a punch biopsy.

• Imaging to assess for disease spread is required only when two or more high-risk features are present. These include lesion diameter > 2 cm, lesion depth of invasion > 6 mm, lesions at the site of a previously treated squame, lesions at previously irradiated sites, and immunocompromised status.

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

Table of Contents

(1) Cutaneous Squamous Cell Carcinoma Risk Factors

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

(3) Diagnostic & Therapeutic Roles of Pathology in Cutaneous Squamous Cell Carcinoma

(4) Imaging in Cutaneous Squamous Cell Carcinoma

Cutaneous Squamous Cell Carcinoma Risk Factors

Genetic and environmental factors influence Squamous Cell Carcinoma (SCC) development. UV exposure, whether from the sun or tanning beds, is the most important environmental risk factor. Patients with less melanin (lower Ftizpatrick number classification) are more susceptible to skin damage from UV radiation. As UV exposure increases across the lifetime, most patients are older (> 60 years) at diagnosis. Other important environmental risk factors include personal history of SCCs, burn injuries, radiation, and immunosuppression. Solid-organ transplant patients are at particularly high risk of SCC. Genetic syndromes associated with the development of SCC include, but are not limited to, xeroderma pigmentosum, Muir Torre Syndrome, Oculocutaneous Albinism, Fanconi Anemia, Dyskeratosis Congentia, Bloom Syndrome, and Werner Syndrome [1].

[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.

Listen to the Full Podcast

Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction with Dr. Gina Jefferson on the BackTable ENT Podcast)
Ep 135 Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction with Dr. Gina Jefferson
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Physical Examination of Patients with Suspected Cutaneous Squamous Cell Carcinoma

A skilled clinician can estimate the extent of disease via physical exam. Lesion size influences tumor staging. Mobility (or lack thereof) can hint at perineural invasion – a poor prognostic factor. Lesion location is important to note, as it dictates the operative plan. Though imaging offers precise insight into nodal spread, palpation of head and neck lymph nodes can offer a rough estimate. Lesions found on the upper two-thirds of the face will drain to the parotid lymph nodes. Lesions found on the lower one-third of the face will drain to perifacial lymph nodes.

[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.

Diagnostic & Therapeutic Roles of Pathology in Cutaneous Squamous Cell Carcinoma

As with other cancers, pathology samples are a prerequisite to diagnosing cutaneous SCC. Excisional biopsy with a 3 mm margin, followed by primary closure, can be both diagnostic and curative for smaller squames. Punch biopsy with a 4 or 5 mm punch is appropriate for larger lesions and lesions located close to critical structures, such as the eye. Many squamous (and basal) cell carcinomas are treatable by a dermatologist performing Mohs surgery – a technique that allows them to survey the entire margin of a given lesion while in the operating room.

When assessing pathology slides, lesion differentiation, perineural invasion (i.e. the involvement of nerves > 0.1 mm in diameter), margin status (for post-surgical patients), and depth of invasion (> 6 mm) are all important prognostic indicators. When considering neck disease of unknown etiology, next-generation sequencing for biomarkers can differentiate cutaneous and mucosal squamous cell cancers.

[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. 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.

Imaging in Cutaneous Squamous Cell Carcinoma

Patients with cutaneous SCC do not require imaging unless two or more high-risk features are present. High-risk features include lesion diameter > 2 cm, lesion depth of invasion > 6mm, lesions at the site of a previously treated squame, lesions at previously-irradiated sites, and an immunocompromised status. Imaging aims to identify occult metastases. Options for imaging include a CT, an MRI, and/or a PET scan. In immunocompromised patients with two or more additional high-risk features, Dr. Jefferson consistently orders PET scans.

[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.

Podcast Contributors

Dr. Gina Jefferson discusses Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction on the BackTable 135 Podcast

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 discusses Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction on the BackTable 135 Podcast

Dr. Ashley Agan

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

Dr. Gopi Shah discusses Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction on the BackTable 135 Podcast

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.

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